Patent Application
20210139442
The presently claimed invention relates to a product of monoesterification obtained from a D-glucaro-6,3-lactone and an alcohol and a process for the preparation of the same.
The saccharic acid or glucaric acid is obtained by oxidizing a sugar such as glucose with nitric acid. The sodium salt of glucaric acid is used in dishwasher detergents. In hard-water the sodium salt of glucaric acid acts as chelating agent for calcium and magnesium ions to make the detergents more efficient. The utility of the sodium salt of glucaric acid has replaced environmentally problematic phosphates in most detergents.
The glucaric acid forms 2 isomers of lactonic acid; (1,4) and (3,6) D-glucaro-lactonic acid. The D-glucaro-6,3-lactonic acid has exceptional stability in aqueous solutions and is not hydrolyzed to corresponding dibasic acid.
Ethyl, propyl, butyl and amyl monoesters of D-saccharic acid were synthesized by Zinner et. al. [Chem Ber 1956, 1503]. The esterification of glucaro-3,6-lactonic acid with an activated cation exchanger and alcohols produces the glucaro-3,6-lactonic acid monoester, which are also characterized as tribenzoates and tris-p-nitrobenzoates.
EP 0 526 301 A1 discloses synthesis of octyl, dodecyl, octadecyl, hexyl glucaro-1,4-lactone monoester, however, there is no indication in said document about the glucaro-6,3-lactone monoester.
L. A. Mai [Institute of Chemistry of the Academy of Science of the Latvian SSR, Vol. 31. No. 8, 1961] discloses process for the synthesis of methyl ester of the glucaro-6,3-lactone monoester from the dilactone.
Heslop and Smith [Journal of Chemical Society, 1944, pages 633-636] discloses process for the synthesis of the methyl ester of glucaro-6,3-lactone monoester from the D-glucosaccharo-1,4,3,6-dilactone.
WO 2016/131672 discloses a process for the preparation of diester from dilactones. WO 2016/131672 describes that the monoester is one of the products formed in this reaction. One of the disadvantages in preparation of D-glucaro-6,3-lactone monoester is the formation of the diester as one of the by-products. The existing techniques for selectively obtaining D-glucaro-6,3-lactone monoester is not satisfactory in terms of low yield and purity of the final product. Moreover, the relatively high yield and selectivity of undesirable product such as di-ester and acid render the available techniques unfavorable.
Thus, it was an object of the presently claimed invention to provide a process for selectively preparing D-glucaro-6,3-lactone monoester having a high purity with process conditions which render the invention economical by optimizing them in a manner that the formation of diester, D-glucaro-1,4-lactone monoester and di-lactone, is either minimized or eliminated.
Surprisingly, it has been found that the reaction between D-glucaro-6,3-lactonic acid and an alcohol of general formula (I) in the presence of an acid catalyst results in an economical and highly selective process to produce D-glucaro-6,3-lactone monoester. The optimized process conditions of the presently claimed invention provide a selective and economical process for the preparation of D-glucaro-6,3-lactone monoester with only traces or without formation of diester, D-glucaro-1,4-lactone monoester and di-lactone.
Accordingly, in one aspect, the presently claimed invention is directed to a process for the selective preparation of D-glucaro-6,3-lactone monoester comprising the steps of: (A) reacting D-glucaro-6,3-lactone with at least one alcohol of a general formula (I)
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
in the presence of at least one mineral acid or at least one Lewis acid or at least one carboxylic acid or at least one sulfonic acid to obtain a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
In another aspect, the presently claimed invention is directed to a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C6-C20 alkyl or
Before the present compositions and formulations of the presently claimed invention are described, it is to be understood that this invention is not limited to particular compositions and formulations described, since such compositions and formulation may, of course, vary. It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the presently claimed invention will be limited only by the appended claims.
If hereinafter a group is defined to comprise at least a certain number of embodiments, this is meant to also encompass a group which preferably consists of these embodiments only. Furthermore, the terms “first”, “second”, “third” or “(a)”, “(b)”, “(c)”, “(d)” etc. and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the presently claimed invention described herein are capable of operation in other sequences than described or illustrated herein. In case the terms “first”, “second”, “third” or “(A)”, “(B)” and “(C)” or “(a)”, “(b)”, “(c)”, “(d)”, “i”, “ii” etc. relate to steps of a method or use or assay there is no time or time interval coherence between the steps, that is, the steps may be carried out simultaneously or there may be time intervals of seconds, minutes, hours, days, weeks, months or even years between such steps, unless otherwise indicated in the application as set forth herein above or below.
Furthermore, the ranges defined throughout the specification include the end values as well i.e. a range of 1 to 10 implies that both 1 and 10 are included in the range. For the avoidance of doubt, applicant shall be entitled to any equivalents according to applicable law.
In the following passages, different aspects of the presently claimed invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the presently claimed invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the presently claimed invention, and form different embodiments, as would be understood by those in the art. For example, in the appended claims, any of the claimed embodiments can be used in any combination.
Accordingly, a process for preparing D-glucaro-6,3-lactone monoester comprises the steps of: (A) reacting D-glucaro-6,3-lactone with at least one alcohol of a general formula (I)
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
wherein n is an integer in the range of 1 to 20,
More preferably, a process for preparing D-glucaro-6,3-lactone monoester comprises the steps of:
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
in the presence of at least one Lewis acid or at least one carboxylic acid or at least one sulfonic acid to obtain a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
Most preferably, a process for preparing D-glucaro-6,3-lactone monoester comprises the steps of:
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
in the presence of at least one Lewis acid or at least one carboxylic acid to obtain a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
In particularly preferably, a process for preparing D-glucaro-6,3-lactone monoester comprises the steps of:
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
in the presence of at least one Lewis acid to obtain a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
In another preferred embodiment, the presently claimed invention is directed to a process for preparing D-glucaro-6,3-lactone monoester comprises the steps of:
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
in the presence of Al(CH3—SO3)3 to obtain a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
D-glucaro-6,3-lactone (formula III)
Oxidation of aldoses, for instance, with bromine-water affects only the aldehyde group, converting it into a carboxyl group. By the term “aldose”, it is referred to a monosaccharide containing only one aldehyde group per molecule. The oxidation products are called aldonic acids, for example D-gluconic acid is obtained from D-glucose. When aldoses are oxidized more strongly, for example with concentrated nitric acid, then the primary alcohol group as well as the aldehyde group are transformed into carboxyl groups. The products are polyhydroxydicarboxylic acids known as aldaric acids.
An example of aldaric acid is the aldaric acid derived from glucose, i.e. D-glucaric acid, also known as saccharic acid. Conventional techniques may be employed for obtaining D-glucaric acid. Such techniques are known to a person skilled in the art. Nevertheless, U.S. Pat. No. 2,472,168 illustrates a method for the preparation of D-glucaric acid from glucose using a platinum catalyst in the presence of oxygen and a base. Other oxidation methods, as disclosed in U.S. Pat. Nos. 6,049,004, 5,599,977, 6,498,269 and 8,669,397, may also be employed.
D-glucaro-6,3-lactone can also be obtained from various available techniques. One such technique is discussed by Chen and Kiely [J. Org. Chem. 1996, 61, 5847-5851], wherein a cation exchange resin is added to a mixture of monopotassium D-glucarate and water. Acid form of cation exchange resin is added further with filtration and concentration carried thereafter. D-glucaro-6,3-lactone is obtained after 2-3 days of crystallization in the form of white solids and used for synthesis of head, tail hydroxylated nylons. Troy et. Al. [J. Org. Chem. 2009, 74, 8373-8376] discloses acidification of calcium D-glucarate tetrahydrate with sulfuric acid in the presence of acetone-water. The acidification step is followed by filtration, reduced pressure operation and concentration steps to finally obtain a concentrated aqueous solution containing solid particles of a mixture of D-glucaric acid, D-glucaro-1,4-lactone, D-glucaro-6,3-lactone and D-glucaro-1,4:6,3-lactone in a fixed ratio. For the purpose of the presently claimed invention, the choice of the D-glucaro-6,3-lactone is not limited to the method used to prepare the same.
A person skilled in the art is aware of such methods and may employ any of the available techniques to obtain the same.
Alcohol of general formula I (R1—OH)
For the purpose of the presently claimed invention, the alcohol of general formula I is
R1—OH (I),
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
In a preferred embodiment, R1 denotes
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
Y denotes O or S; and
more preferably R1 is
even more preferably R1 is
most preferably R1 is
particular preferably R1 is
Within the context of the presently claimed invention, the term “alkyl”, as used herein, refers to an acylic saturated aliphatic groups, including linear or branched alkyl saturated hydrocarbon radical denoted by a general formula CnH2n+1 and wherein n is the number of carbon atoms 1, 2, 3, 4 etc.
In a preferred embodiment the unsubstituted, linear or branched, C1-C20 alkyl refers to a branched or unbranched saturated hydrocarbon group having C1-C20 carbon atoms, more preferably C2-C20 carbon atoms, even more preferably C3-C20 carbon atoms, most preferably C4-C20 carbon atoms, particularly preferably C5-C20 carbon atoms, even more particularly preferably C6-C20 carbon atoms.
In a preferred embodiment, R1 denotes unsubstituted linear C1-C20 alkyl which preferably selected from the group consisting of, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl and eicosyl; more preferably selected from the group consisting of hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl and eicosyl.
In a preferred embodiment, R1 denotes unsubstituted branched C1-C20 alkyl which is selected from the group consisting of, but are not limited to, isopropyl, iso-butyl, neo-pentyl, 2-ethyl-hexyl, 2-propyl-heptyl, 2-butyl-octyl, 2-pentyl-nonyl, 2-hexyl-decyl, iso-hexyl, iso-heptyl, iso-octyl, iso-nonyl, iso-decyl, iso-dodecyl, iso-tetradecyl, iso-hexadecyl, iso-octadecyl and iso-eicosyl, more preferably selected from the group consisting of 2-ethyl-hexyl, 2-propyl-heptyl, 2-butyl-octyl, 2-pentyl-nonyl, 2-hexyl-decyl, iso-hexyl, iso-heptyl, iso-octyl, iso-nonyl, iso-decyl, iso-dodecyl, iso-tetradecyl, iso-hexadecyl, iso-octadecyl and iso-eicosyl.
In a preferred embodiment, R1 denotes unsubstituted, linear or branched alkenyl preferably selected from C2-C20 carbon atoms, more preferably C3-C20 carbon atoms, even more preferably C4-C20 carbon atoms, most preferably C5-C20 carbon atoms, particularly preferably C6-C20 carbon atoms, having at least one C═C double bond in any position, preferably, 1 to 5 C═C double bonds, more preferably 1 to 4 C═C double bonds, even more preferably 1 to 3 C═C double bonds, most preferably 1 to 2 C═C double bonds, particular preferably 1 C═C double bond, wherein each case, each of the carbon atoms is involved not in more than 1 double bond.
Representative examples of C2-C20 alkenyl containing at least one double bond include, but are not limited to, 1-propenyl, 1-butenyl, 1-pentenyl, 1-hexenyl, 2-hexenyl, 1-heptenyl, 2-heptenyl, 1-octenyl, 2-octenyl, 1-nonenyl, 2-nonenyl, 1-decenyl, 2-decenyl, 1-undecenyl, 2-undecenyl, 1-dodecenyl, 2-dodecenyl, 1-tridecenyl, 2-tridecenyl, 1-tetradecenyl, 2-tetradecenyl, 1-pentadecenyl, 2-pentadecenyl, 1-hexadecenyl, 2-hexadecenyl, 1-heptadecenyl, 2-heptadecenyl, 1-octadecenyl, 2-octadecenyl, 1-nonadecenyl, 2-nonadecenyl, 1-eicosenyl and 2-eicosenyl, more preferably selected from 1-hexenyl, 2-hexenyl, 1-heptenyl, 2-heptenyl, 1-octenyl, 2-octenyl, 1-nonenyl, 2-nonenyl, 1-decenyl, 2-decenyl, 1-undecenyl, 2-undecenyl, 1-dodecenyl, 2-dodecenyl, 1-tridecenyl, 2-tridecenyl, 1-tetradecenyl, 2-tetradecenyl, 1-pentadecenyl, 2-pentadecenyl, 1-hexadecenyl, 2-hexadecenyl, 1-heptadecenyl, 2-heptadecenyl, 1-octadecenyl, 2-octadecenyl, 1-nonadecenyl, 2-nonadecenyl, 1-eicosenyl and 2-eicosenyl.
For the purpose of the presently claimed invention, the representative examples of C2-C20-alkenyl containing two double bonds include, but are not limited to, 1,4-hexadienyl, 1,3-hexadienyl, 2,5-hexadienyl, 3,5-hexadienyl, 2,4-hexadienyl etc.
For the purpose of the presently claimed invention, the representative examples of C2-C20-alkenyl containing three double bonds include, but are not limited to, 1,3,5-hexatrienyl, 1,3,6-heptatrienyl, 1,4,7-octatrienyl or 2-methyl-1,3,5hexatrienyl etc.
For the purpose of the presently claimed invention, the representative examples of C2-C20-alkenyl containing four double bonds include, but are not limited to, 1,3,5,7-octatetraenyl, 1,3,5,8-nonatetraenyl, 1,4,7,10-undecatetraenyl, 2-ethyl-1,3,6,8-nonatetraenyl, 2-ethenyl-1,3,5,8-nonatetraenyl etc., and
For the purpose of the presently claimed invention, the representative examples of C2-C20-alkenyl containing five double bonds include, but are not limited to, 1,3,5,7,9-decapentaenyl, 1,4,6,8,10-undecapentaenyl, 1,4,6,9,11-dodecapentaenyl etc.
For the purpose of the presently claimed invention, the term unsubstituted or branched C3-C10 cycloalkyl refers to a monocyclic and bicyclic 3 to 10 membered saturated cycloaliphatic radical.
In a preferred embodiment, R1 denotes unsubstituted or branched C3-C10 cycloalkyl is monocyclic and bicyclic preferably selected from C3-C10, more preferably C4-C10, most preferably C5-C10, particular preferably C6-C10
Representative examples of unsubstituted or branched C3-C10 monocyclic and bicyclic cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2.1]heptyl and bicyclo[3.1.1]heptyl.
The C3-C10 monocyclic and bicyclic cycloalkyl can be further branched with one or more equal or different alkyl groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, n-pentyl, iso-pentyl, neo-pentyl etc. The representative examples of branched C3-C10 monocyclic and bicyclic cycloalkyl include, but are not limited to methyl cyclohexyl, dimethyl cyclohexyl etc.
In a preferred embodiment, R1 denotes unsubstituted or branched C3-C10 cycloalkenyl refers to a to a monocyclic and bicyclic 3 to 10 membered unsaturated cycloaliphatic radical, more preferably C4-C10, most preferably C5-C10, articular preferably C6-C10, which comprises one or more double bonds. Representative examples of C3-C10 cycloalkenyl include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononenyl or cyclodecenyl. These radicals can be branched with one or more equal or different alkyl radical, preferably with methyl, ethyl, n-propyl or iso-propyl. The representative examples of branched C3-C10 monocyclic and bicyclic cycloalkenyl include, but are not limited to methyl cyclohexenyl, dimethyl cyclohexenyl etc.
Within the context of the present invention, the term alkylene refers to acyclic saturated hydrocarbon chains, which combine different moieties. Representative examples of the alkylene groups include, but are not limited to, —CH2—CH2—, —CH2—CH(CH3)—, —CH2—CH(CH2CH3)—, —CH2—CH(n-C3H7)—, —CH2—CH(n-C4H9)—, —CH2—CH(n-C5H11)—, —CH2—CH(n-C6H13)—, —CH2—CH(n-C7H15)—, —CH2—CH(n-C8H17)—, —CH(CH3)—CH(CH3)—, —(CH2)3—, —(CH2)4—, —(CH2)5—, —(CH2)6—, —(CH2)8—, —(CH2)10—, —C(CH3)2—, —CH2—C(CH3)2—CH2—, and —CH2—[C(CH3)2]2—CH2—. Preferred C2- C10-alkylene are —CH2—CH2—, —CH2—CH(CH3)—, —CH2—CH(CH2CH3)—, —CH2—CH(n-C3H7)—, —CH2—CH(n-C4H9)—, —CH2—CH(n-C6H13)—, and —(CH2)4—.
In a preferred embodiment, R1 denotes unsubstituted C1-C10 alkylene C3-C10 cycloalkyl refers to acyclic saturated hydrocarbon chains, which combine a C3-C10 cycloalkyl group. Alkylene chains can be branched or linear and are unsubstituted and include as in the case of C1-C10 alkylene 1 to 10 carbon atoms or as in the case of C1-C6 alkylene 1 to 6 carbon atoms. C3-C10 cycloalkyl refers to a monocyclic and bicyclic 3 to 10 membered saturated cycloaliphatic radical, more preferably C4-C10, even more preferably C5-C10, most preferably C5-C10, particular preferably C6-C10.
Representative examples of unsubstituted C1-C10 alkylene C3-C10 cycloalkyl include, but are not limited to, —CH2—(C3H5), —CH2—(C4H7), —CH2—(C5H9), —CH2—(C6H11), —CH2—(C7H13), —CH2—CH2(C3H5), —CH2—CH2(C4H), —CH2—CH2(C5H9), —CH2—CH2(C6H11), —CH2—CH(C7H13)—, —CH2—CH(C6H11)—, —CH2—CH(C5H9).
In a preferred embodiment, R1 denotes unsubstituted C1-C10 alkylene C3-C10 cycloalkenyl refers to acyclic saturated hydrocarbon chains, which combine a C3-C10 cycloalkenyl group. Alkylene chains can be branched or linear and are unsubstituted and include as in the case of C1-C10 alkylene 1 to 10 carbon atoms or as in the case of C1-C6 alkylene 1 to 6 carbon atoms. C3-C10 cycloalkenyl refers to a monocyclic and bicyclic 3 to 10 membered unsaturated cycloaliphatic radical, more preferably C4-C10, even more preferably C5-C10, most preferably C5-C10, particular preferably C6-C10 having at least one C═C double bond.
Representative examples of unsubstituted C1-C10 alkylene C3-C10 cycloalkenyl include, but are not limited to, —CH2—(C3H3), —CH2—(C4H5), —CH2—(C5H7), —CH2—(C6H9), —CH2—(C7H11), —CH2—CH(C5H7), —CH2—CH2(C6H9), —CH2—CH(C7H11), —CH2—CH(C7H9)—, —CH2—CH(C6H7)—, —CH2—CH(C5H5)—.
In a preferred embodiment, R1 denotes —(CH2CH2O)nH, wherein n is an integer in the range of 1 to 20, preferably in the range of 2 to 10, more preferably 2 to 7, even more preferably 2 to 6, most preferably 3 to 6 and particular preferably 3 to 5. Representative examples of —(CH2CH2O)nH include, but are not limited to, —(CH2O)2H, —(CH2CH2O)3H, —(CH2CH2O)4H, —(CH2CH2O)5H, —(CH2CH2O)6H, —(CH2CH2O)12H, —(CH2CH2O)15H etc.
In a preferred embodiment, R1 denotes —(CH2)nYR2. Within the context of the presently claimed invention, the term ‘n’ is an integer selected from 1 to 20, preferably from 1 to 15, more preferably from 1 to 10, and particular preferably 1 to 6. Within the context of the presently claimed invention, Y denotes O or S, more preferably Y denotes 0.
In a preferred embodiment, R2 denotes
For the purpose of the presently claimed invention, the term unsubstituted, linear or branched, C1-C20 alkyl or unsubstituted, linear or branched, C2-C20 alkenyl or unsubstituted or branched C3-C10 cycloalkyl or unsubstituted or branched C3-C10 cycloalkenyl or unsubstituted C1-C10 alkylene C3-C10 cycloalkyl or unsubstituted C1-C10 alkylene C3-C10 cycloalkenyl have same definitions as stated above.
Acids
In a preferred embodiment, in step (A) the at least one acid is selected from the group consisting of mineral acids, Lewis acids, carboxylic acid and sulfonic acids, more preferably the at least one acid is selected from the group consisting of mineral acids, Lewis acids and sulfonic acids, even more preferably the at least one acid is selected from the group consisting of mineral acids and Lewis acids and most preferably the at least one acid is Lewis acid.
In another preferred embodiment, the mineral acid is selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid, nitric acid, nitrous acid, sulphurous acid, chloric acid, chlorous acid and hypochlorous acid, more preferably the mineral acid is selected from sulfuric acid and hydrochloric acid, even more preferably the mineral acid is sulfuric acid.
In another preferred embodiment, the Lewis acid is a metal-containing compound selected from the group consisting of
a) AsX3, GaX3, BX3, BX3.(C2H5)2O, BX3—S(CH3)2, AlX3, (C2H5)2AlX, SbX3, SbX5, SnX2, MgX2, MgX2.O(C2H5)2, ZnX2, BiX3, FeX2, TiX2, TiX4, NbX5, NiX2, CoX2, HgX2, whereby X in each case denotes F, C, Br, SO3, CF3—SO3, CH3—SO3, or I;
b) BH3, B(CH3)3, GaH3, AlH3, Al(acetate)(OH)2, Al[OCH(CH3)2]3, Al(OCH3)3, Al(OC2H5)3, Al2O3, (CH3)3Al, Ti[OCH(CH3)2]3Cl, Ti[OCH(CH3)2]4, methylaluminum di-(2,6-di-tert-butyl-4-methylphenoxide), methylaluminum di-(4-brom-2,6-di-tert-butylphenoxide), LiClO4;
c) Mg(acetate)2, Zn(acetate)2, Ni(acetate)2, Ni(NO3)2, Co(acetate)2, Co(NO3)2, Cu(acetate)2, Cu(NO3)2, Li(acetate), Zr(acetylacetonate)4, Si(acetate)4, K(acetate), Na(acetate), Cs(acetate), Rb(acetate), Mn(acetate)2, Fe(acetate)2, Bi(acetate)3, Sb(acetate)3, Sr(acetate)2, Sn(acetate)2, Zr(acetate)2, Ba(acetate)2, Hg(acetate)2, Ag(acetate), Tl(acetate)3, Sc(fluoromethansulfonate)3, Ln(fluoromethanesulfonate)3, Ni(fluoromethanesulfonate)2, Ni(tosylate)2, Co(fluoromethanesulfonate)2, Co(tosylate)2, Cu(fluoromethanesulfonate)2 and Cu(tosylate)2; more preferably the Lewis acid is selected form the group consisting of
a) BX3, BX3—(C2H5)2O, BX3—S(CH3)2, AlX3, (C2H5)2AlX, TiX4 whereby X in each case denotes F, Cl, Br, SO3, CF3—SO3, CH3—SO3, or I;
b) BH3, B(CH3)3, AlH3, Al(acetate)(OH)2, Al[OCH(CH3)2]3, Al(OCH3)3, Al(OC2H5)3, Al2O3, (CH3)3Al, Ti[OCH(CH3)2]3Cl, Ti[OCH(CH3)2]4, methylaluminum di-(2,6-di-tert-butyl-4-methylphenoxide), methylaluminum di-(4-brom-2,6-di-tert-butylphenoxide);
c) Sc(fluoromethansulfonate)3, Ln(fluoromethanesulfonate)3, Ni(fluoromethanesulfonate)2, Co(fluoromethanesulfonate)2, Cu(fluoromethanesulfonate)2;
most preferably the Lewis acid is selected form the group consisting of BX3, BX3.S(CH3)2, AlX3, and TiX4, whereby X in each case denotes F, Cl, CF3—SO3, or CH3—SO3, particular preferably the Lewis acid is AlX3, whereby X denotes F, Cl, CF3—SO3, or CH3—SO3.
In a preferred embodiment, the carboxylic acid is selected from the group consisting of trifluoroacetic acid, difluoroacetic acid, fluoroacetic acid, trichloroacetic acid, dichloroacetic acid, monochloroacetic, tribromoacetic acid, dibromoacetic acid, bromoacetic acid and iodoacetic acid. More preferably, the carboxylic acid is selected from the group consisting of trifluoroacetic acid, difluoroacetic acid, fluoroacetic acid, trichloroacetic acid, dichloroacetic acid, monochloroacetic, tribromoacetic acid, dibromoacetic acid and bromoacetic acid. Even more preferably, the carboxylic acid is selected from the group consisting of trifluoroacetic acid, difluoroacetic acid, fluoroacetic acid, trichloroacetic acid, dichloroacetic acid, monochloroacetic and tribromoacetic acid. Most preferably, the carboxylic acid is selected from the group consisting of trifluoroacetic acid, difluoroacetic acid, trichloroacetic acid and dichloroacetic acid. In particularly preferably, the carboxylic acid is selected from the group consisting of trifluoroacetic acid, difluoroacetic acid and trichloroacetic acid. Even in particularly preferably, the carboxylic acid is trifluoroacetic acid.
In a preferred embodiment, the sulfonic acid is selected from the group consisting of methanesulfonic acid, ethanesulfonic acid, 1-propanesulfonic acid, 1-butanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, p-xylene-2-sulfonic acid, naphathalene-1-sulfonic acid and naphthalene-2-sulfonic acid, more preferably the sulfonic acid is selected from the group consisting of methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid, even more preferably methanesulfonic acid and p-toluenesulfonic acid.
Molecular Sieve
In a preferred embodiment, the process of the presently claimed invention is carried out in the presence of one or more molecular sieves. Where the process of the presently claimed invention is carried out in the presence of one or more molecular sieves, preference is given to using one to three molecular sieves, more preferably one or two molecular sieves, even more preferably one (1) molecular sieve. Examples of suitable molecular sieves are molecular sieves having a pore size in the range from 0.1 to 10 angstroms, preferably 3 to 7 angstroms, more preferably 3 to 6 angstroms, very preferably 3 to 4 angstroms.
In a preferred embodiment of the presently claimed invention, the process of the presently claimed invention is carried out in the presence of a molecular sieve having a pore size of 3 angstroms, and the molecular sieve having a pore size of 3 angstroms and the compound of formula (III) are used in general in a weight ratio of 1:10 to 10:1, preferably of 1:1 to 5:1, more preferably of 1.5:1 to 4:1, very preferably of 2:1 to 3:1.
An advantage of using one or more molecular sieves, more particularly of using a molecular sieve having a pore size of 3 angstroms, is its ability to take up liberated water molecules, and in doing so remove water from the equilibrium.
Polar Aprotic Solvent
In a preferred embodiment, the process is carried out in presence of at least one polar aprotic solvent.
Within the context of the presently claimed invention, the term “polar aprotic solvent” refers to an organic solvent having a dipole moment in the range of 0.2 to 5, more preferably in the range of 0.2 to 3, most preferably in the range of 0.2 to 2 and a water solubility of at least about 5% (volume) at ambient temperature, i.e., about 20° C., and which does not undergo significant hydrogen exchange at approximately neutral pH, i.e., in the range of 5 to 9, or preferably in the range 6 to 8.
In another preferred embodiment, the at least one polar aprotic solvent is selected from the group consisting of ethers, lactones, carbonates, sulfones, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dimethylsulfoxide, N-methyl-pyrrolidone and N-ethyl-pyrrolidone; more preferably the at least one polar aprotic solvent is selected from the group consisting of ethers, acetonitrile, dimethylsulfoxide, N-methyl-pyrrolidone, even more preferably the at least one polar aprotic solvent is selected from the group consisting of ethers, dimethylsulfoxide, N-methyl-pyrrolidone, most preferably the at least one polar aprotic solvent is an ether.
Within the context of the presently claimed invention, the ether is preferably selected from the group consisting of methyl tert-butyl ether, dioxane, diethoxy methane, dimethoxy methane, tetrahydrofuran and tetrahydropyran, more preferably the ether is selected from tetrahydrofuran and dioxane, even more preferably the ether is dioxane.
The weight ratio between the at least one polar aprotic solvent and the D-glucaro-3,6-lactone is preferably in the range of ≥30:1 to ≤1:1. More preferably, the ratio is in the range of ≥20:1 to ≤1:1, or ≥10:1 to ≤1:1, or ≥8:1 to ≤2:1, or ≥5:1 to ≤2:1, or ≥3:1 to ≤2:1. Even more preferably, it is in the range of ≥20:1 to ≤1:1, or ≥10:1 to ≤1:1, or ≥8:1 to ≤2:1, or ≥5:1 to ≤2:1, or ≥3:1 to ≤2:1. Most preferably, in the range of ≥10:1 to ≤1:1, or ≥8:1 to ≤2:1, or ≥5:1 to ≤2:1.
In a preferred embodiment, the molar ratio between the at least one alcohol of general formula (I) and D-glucaro-6,3-lactone is in the range of ≥0.1:1 to ≤5:1, more preferably in the range of ≥0.5:1 to ≤2:1, even more preferably in the range of ≥0.8:1 to ≤2:1, most preferably 1:1.
In a preferred embodiment, the at least one acid is present in the process in an amount in the range of ≥0.01 mol.-% to ≤20 mol.-%, more preferably in the range of ≥0.01 mol.-% to ≤10 mol.-%, even more preferably in the range of ≥0.01 mol.-% to ≤5 mol.-%, most preferably in the range of ≥0.05 mol.-% to ≤2 mol.-%, particular preferably in the range of ≥0.08 mol.-% to ≤0.5 mol.-%, in each case is in relation to the D-glucaro-6,3-lactone
In another embodiment, the process of the presently claimed invention is carried out at a temperature in the range of ≥30° C. to ≤90° C., more preferably ≥50° C. to ≤80° C., most preferably ≥60° C. to ≤80° C., and particular preferably in the range of ≥65° C. to ≤75° C. The alcohol of general formula (I) and D-glucaro-6,3-lactone form a homogenous mixture upon adding into the polar aprotic solvent. To the thus obtained homogenous mixture the at least one acid catalyst is added. The solution obtained after addition of the at least one acid catalyst is homogenous or heterogenous. This mixture is heated to a temperature in the range of ≥30° C. to ≤90° C. For carrying out the heating to a temperature in the range of ≥30° C. to ≤90° C., any suitable techniques can be used. A person skilled in the art is aware of such techniques.
The compound of formula (II) formed in the reaction is isolated by any method known in the art selected from the group consisting of chemical separation, acid-base neutralization, distillation, evaporation, column chromatography, filtration, concentration, crystallization and re-crystallization or a combination thereof. A person skilled in the art is aware of such techniques.
Accordingly, in an embodiment the compound of general formula (II) as obtained according to the process of the presently claimed invention has a general structure as shown herein below
R1 denotes unsubstituted, linear or branched, C6-C20 alkyl or
Accordingly, in a preferred embodiment the compound of general formula (II) obtained by the above described process is Decyl-D-glucaro-6,3-lactone monoester (decyl(2R)-2-[(2S,3R,4S)-3,4-dihydroxy-5-oxo-tetrahydrofuran-2-yl]-2-hydroxy-acetate) and is represented as shown below.
Accordingly, in a preferred embodiment the compound of general formula (II) obtained by the above described process is Dodecyl-D-glucaro-6,3-lactone monoester [dodecyl(2R)-2-[(2S,3R,4S)-3,4-dihydroxy-5-oxo-tetrahydrofuran-2-yl]-2-hydroxy-acetate] and is represented as shown below.
Accordingly, in a preferred embodiment the compound of general formula (II) obtained by the above described process is Tetradecyl-D-glucaro-6,3-lactone monoester [tetradecyl(2R)-2-[(2S,3R,4S)-3,4-dihydroxy-5-oxo-tetrahydrofuran-2-yl]-2-hydroxy-acetate] and is represented as shown below.
Accordingly, in a preferred embodiment the compound of general formula (II) obtained by the above described process is Octyl-D-glucaro-6,3-lactone monoester [octyl(2R)-2-[(2S,3R,4S)-3,4-dihydroxy-5-oxo-tetrahydrofuran-2-yl]-2-hydroxy-acetate] and is represented as shown below.
Accordingly, in a preferred embodiment the compound of general formula (II) obtained by the above described process is Hexadecyl-D-glucaro-6,3-lactone monoester [hexadecyl(2R)-2-[(2S,3R,4S)-3,4-dihydroxy-5-oxo-tetrahydrofuran-2-yl]-2-hydroxy-acetate] and is represented as shown below.
Another aspect of the presently claimed invention relates to the compounds of general formula (II)
R1 denotes unsubstituted, linear or branched, C6-C20 alkyl or
The preferred embodiments of the inventively claimed process also apply to the inventively claimed compounds.
The presently claimed invention offers one or more of following advantages:
The novel synthesis route, as described hereinabove, has several advantages over the current state of the art. The current state of the art available, such as but not limited to the one described by, Zenner et. al [Institute of Organic Chemistry at the University of Rostock, Mar. 12, 1956] reports to have obtained monoester of D-glucaric acid with nearly 47 mol. equivalents of the alcohol used therein. However, surprisingly the novel synthesis route of the presently claimed process provides D-glucaro-(6,3) lactone monoester even at very low mol. equivalent, such as those described hereinabove, with traces or without formation of the by-products and/or unwanted impurities. Another advantage of the presently claimed invention is that a very low quantity of alcohol is used as well as the use of easily available raw materials, such as but not limited to, the at least one polar aprotic solvent, as described hereinabove.
In the following, specific embodiments of the presently claimed invention are described:
1. A process for preparing D-glucaro-6,3-lactone monoester comprising the steps of:
(A) reacting D-glucaro-6,3-lactone with at least one alcohol of a general formula (I)
R1—OH (I),
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
in the presence of at least one mineral acid or at least one Lewis acid or at least one carboxylic acid or at least one sulfonic acid to obtain a compound of general formula (II)
wherein
R1 denotes unsubstituted, linear or branched, C1-C20 alkyl or
2. The process according to embodiment 1, characterized in that unsubstituted, linear C1-C20 alkyl is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, octadecyl, heptadecyl, octadecyl, nonadecyl and eicosyl.
3. The process according to embodiment 1, characterized in that unsubstituted, branched C1-C20 alkyl is selected from the group consisting of iso-propyl, iso-butyl, t-butyl, iso-pentyl, neo-pentyl, 2-ethyl-hexyl, 2-propyl-heptyl, 2-butyl-octyl, 2-pentyl-nonyl, 2-hexyl-decyl, iso-hexyl, iso-heptyl, iso-octyl, iso-nonyl, iso-decyl, iso-dodecyl, iso-tetradecyl, iso-hexadecyl, iso-octadecyl and iso-eicosyl.
4. The process according to embodiment 1, characterized in that R1 denotes
5. The process according to embodiment 4, characterized in that R1 denotes
6. The process according to embodiment 4, characterized in that R1 denotes
7. The process according to embodiment 4, characterized in that R1 denotes
8. The process according to embodiment 1, characterized in that in step (A) the at least one mineral acid is selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid, nitric acid, nitrous acid, sulphurous acid, chloric acid, chlorous acid and hypochlorous acid.
9. The process according to embodiment 8, characterized in that in step (A) the at least one mineral acid is sulfuric acid
10. The process according to embodiment 1, characterized in that in step (A) the at least one Lewis acid is a metal-containing compound selected from the group consisting of
a) AsX3, GaX3, BX3, BX3.(C2H5)2O, BX3—S(CH3)2, AlX3, (C2H5)2AlX, SbX3, SbX5, SnX2, MgX2, MgX2O(C2H5)2, ZnX2, BiX3, FeX2, TiX2, TiX4, NbX5, NiX2, CoX2, HgX2, whereby X in each case denotes F, C, Br, SO3, CF3—SO3, CH3—SO3, or I,
b) BH3, B(CH3)3, GaH3, AlH3, Al(acetate)(OH)2, Al[OCH(CH3)2]3, Al(OCH3)3, Al(OC2H5)3, Al2O3, (CH3)3Al, Ti[OCH(CH3)2]3Cl, Ti[OCH(CH3)2]4, methylaluminum di-(2,6-di-tert-butyl-4-methylphenoxide), methylaluminum di-(4-brom-2,6-di-tert-butylphenoxide), LiClO4,
c) Mg(acetate)2, Zn(acetate)2, Ni(acetate)2, Ni(NO3)2, Co(acetate)2, Co(NO3)2, Cu(acetate)2, Cu(NO3)2, Li(acetate), Zr(acetylacetonate)4, Si(acetate)4, K(acetate), Na(acetate), Cs(acetate), Rb(acetate), Mn(acetate)2, Fe(acetate)2, Bi(acetate)3, Sb(acetate)3, Sr(acetate)2, Sn(acetate)2, Zr(acetate)2, Ba(acetate)2, Hg(acetate)2, Ag(acetate), Tl(acetate)3, Sc(fluoromethansulfonate)3, Ln(fluoromethanesulfonate)3, Ni(fluoromethanesulfonate)2, Ni(tosylate)2, Co(fluoromethanesulfonate)2, Co(tosylate)2, Cu(fluoromethanesulfonate)2 and Cu(tosylate)2.
11. The process according to embodiment 10, characterized in that the at least one Lewis acid is selected from the group consisting of BX3, BX3.S(CH3)2, AlX3, SbX3, and TiX4, whereby X in each case denotes F, Cl, CF3—SO3, or CH3—SO3.
12. The process according to embodiment 10 or 11, characterized in that in step (A) the at least one Lewis acid is Al(CH3—SO3)3.
13. The process according to embodiment 1, characterized in that in step (A) the at least one carboxylic acid is selected from the group consisting of trifluoroacetic acid, difluoroacetic acid, fluoroacetic acid, trichloroacetic acid, dichloroacetic acid, monochloroacetic, tribromoacetic acid, dibromoacetic acid, bromoacetic acid and iodoacetic acid.
14. The process according to embodiment 1, characterized in that in step (A) the at least one sulfonic acid is selected from the group consisting of methanesulfonic acid, ethanesulfonic acid, 1-propanesulfonic acid, 1-butanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, p-xylene-2-sulfonic acid, naphathalene-1-sulfonic acid and naphthalene-2-sulfonic acid.
15. The process according to one or more of embodiments 1 to 14, characterized in that step (A) is carried out in the presence of a molecular sieve.
16. The process according to embodiment 15, characterized in that in step (A) the molecular sieve has a pore diameter in the range of ≥0.1 Å to ≤10 Å.
17. The process according to embodiments 1 to 7, wherein step (A) is carried out in presence of at least one polar aprotic solvent.
18. The process according to embodiment 17, characterized in that the at least one polar aprotic solvent is selected from the group consisting of ethers, lactones, carbonates, sulfones, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dimethylsulfoxide, N-methyl-pyrrolidone and N-ethyl-pyrrolidone.
19. The process according to embodiment 18, characterized in that the at least one ether is selected from the group consisting of methyl tert-butyl ether, dioxane, diethoxy methane, dimethoxy methane, tetrahydrofuran and tetrahydropyran.
20. The process according to embodiment 19, characterized in that the at least one ether is dioxane.
21. The process according to one or more of embodiments 1 to 20, characterized in that in step (A) the molar ratio between the at least one alcohol of general formula (I) and D-glucaro-6,3-lactone is in the range of ≥0.1:1 to ≤5:1.
22. The process according to one or more of embodiments 1 to 13, characterized in that in step (A) the at least one acid is present in an amount in the range of ≥0.01 mol.-% to ≤20 mol.-% in relation to the D-glucaro-6,3-lactone.
23. The process according to one or more of embodiments 1 to 22, characterized in that in step (A) the molecular sieve is present in an amount in the range of ≥10 wt.-% to ≤40 wt.-% in relation to the of D-glucaro-6,3-lactone.
24. The process according to one or more of embodiments 1 to 23, characterized in that the weight ratio between the at least one polar aprotic solvent and D-glucaro-6,3-lactone is in the range of ≥1:1 to ≤10:1.
25. The process according to one or more of embodiments 1 to 24, characterized in that in step (A) the reaction is carried out by stirring at a rotational speed in the range of ≥100 rpm to ≤500 rpm for a period in the range of ≥1 h to ≤10 h.
26. The process according to one or more of embodiments 1 to 25, characterized that step (A) is carried out at a temperature in the range of ≥30° C. to ≤90° C.
27. A compound of general formula (II)
R1 denotes unsubstituted, linear or branched, C6-C20 alkyl or
28. The compound of formula (II) according to embodiment 27 is selected from the group consisting of
While the presently claimed invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the presently claimed invention.
Chemicals:
are available from Sigma Aldrich.
General Procedure for Synthesis of D-Glucaro-6,3-Lactone Monoester:
D-glucaro-6,3-monolactone (96.1% purity, 0.65 mol, 131 g), alcohol (1.0 equiv., 0.65 mol), aluminum methanesulfonate (0.1 equiv., 0.065 mol, 20.4 g), optionally molecular sieves 3 Å (28 g) and dioxane (360 g) were charged to a reaction flask. The mixture was stirred at 50-80° C. until completion of the reaction. The reaction mass was added to 200 mL of 5% aqueous sodium bicarbonate solution and the organic layer was separated. The organic layer was washed with water, dried over anhydrous sodium sulfate and then concentrated to yield crude product. The crude product was isolated by crystallization using a suitable solvent to obtain the desired D-glucaro-6,3-lactone monoester.
Above reaction was carried out similarly using decanol (0.65 moles) as alcohol. The product was crystallized from heptane to obtain the desired decyl-D-glucaro-6,3-lactone monoester (29 g).
1H NMR (500 MHz, DMSO-d6, TMS): δ 6.18-6.16 (d, 1H), δ 5.89-5.86 (d, 1H), δ 5.47-5.46 (d, 1H), δ 4.51-4.44 (m, 2H), δ 4.26-4.21 (t, 2H), δ 4.06-4.05 (d, 2H), δ 1.58-1.56 (d, 2H), δ 1.25 (bs, 14H), δ 0.85-8.83 (t, 3H).
13C NMR (500 MHz, DMSO-d6, TMS): δ 175.8, δ 170.1, δ 80, δ 70.1, δ 69.6, δ 69.2, δ 64.2, δ 31.2, δ 28.94, δ 28.93, δ 28.68, δ 28.66, δ 27.9, δ 25.2, δ 22, δ 13.8.
Above reaction was carried out similarly using dodecanol (0.05205 moles) as alcohol. The product was crystallized from heptane to obtain the desired dodecyl-D-glucaro-6,3-lactone monoester (1.8 g).
1H NMR (500 MHz, DMSO-d6, TMS): δ 6.19-6.17 (d, 1H), δ 5.89-5.87 (d, 1H), δ 5.48-5.46 (d, 1H), δ 4.51-4.43 (m, 2H), δ 4.25-4.18 (t, 2H), δ 4.08-4.03 (m, 2H), δ 1.60-1.56 (t, 2H), δ 1.24 (bs, 18H), δ 0.87-8.83 (t, 3H).
13C NMR (500 MHz, DMSO-d6, TMS): δ 175.8, δ 170.1, δ 80, δ 70.1, δ 69.6, δ 69.2, δ 64.2, δ 31.2, δ 29, δ 28.99, δ 28.91, δ 28.69, δ 28.65, δ 27.9, δ 25.2, δ 22, δ 13.9.
Above reaction was carried out similarly using tetradecanol (0.05205 moles) as alcohol. The product was crystallized from dichloromethane to obtain the desired tetradecyl-D-glucaro-6,3-lactone monoester (1.3 g).
1H NMR (500 MHz, DMSO-d6, TMS): δ 6.18-6.17 (d, 1H), δ 5.88-5.87 (d, 1H), δ 5.47-5.46 (d, 1H), δ 4.51-4.45 (m, 2H), δ 4.25-4.20 (t, 2H), δ 4.09-4.02 (d, 2H), δ 1.60-1.58 (d, 2H), δ 1.28 (bs, 22H), δ 0.87-8.85 (t, 3H).
13C NMR (500 MHz, DMSO-d6, TMS): δ 176.3, δ 170.6, δ 80.5, δ 70.6, δ 70.1, δ 69.7, δ 64.7, δ 31.7, δ 29.5, δ 29.48, δ 29.42, δ 29.18, δ 29.15, δ 28.4, δ 25.7, δ 22.5, δ 14.4.
Above reaction was carried out similarly using octanol (0.26025 moles) as alcohol. The product was crystallized from heptane to obtain the desired octyl-D-glucaro-6,3-lactone monoester (6 g).
1H NMR (500 MHz, DMSO-d6, TMS): δ 6.17-6.16 (d, 1H), δ 5.87-5.86 (d, 1H), δ 5.46-5.45 (d, 1H), δ 4.50-4.44 (m, 2H), δ 4.25-4.20 (t, 2H), δ 4.10-4.02 (d, 2H), δ 1.61-1.56 (d, 2H), δ 1.25 (bs, 10H), δ 0.87-8.85 (t, 3H).
13C NMR (500 MHz, DMSO-d6, TMS): δ 176.3, δ 170.6, δ 80.5, δ 70.6, δ 70.1, δ 69.7, δ 61.1, δ 31.7, δ 29.2, δ 29.1, δ 29, δ 28.4, δ 25.7, δ 22.5, δ 14.4.
Above reaction was carried out similarly using hexadecanol (0.26025 moles) as alcohol. The product was crystallized using suitable solvent to obtain desired hexadecyl-D-glucaro-6,3-lactone monoester (0.5 g).
1H NMR (500 MHz, DMSO-d6, TMS): δ 6.22-6.21 (d, 1H), δ 5.93-5.91 (d, 1H), δ 5.51-5.50 (d, 1H), δ 4.56-4.49 (m, 2H), δ 4.30-4.25 (t, 2H), δ 4.13-4.08 (d, 2H), δ 1.65-1.62 (d, 2H), δ 1.3 (s, 26H), δ 0.9-8.88 (t, 3H).
13C NMR (500 MHz, DMSO-d6, TMS): δ 176.3, δ 170.6, δ 80.5, δ 70.6, δ 70.1, δ 69.7, δ 64.7, δ 31.7, δ 29.5, δ 29.48, δ 29.42, δ 29.18, δ 29.15, δ 28.4, δ 25.7, δ 22.5, δ 14.4.
| Number | Date | Country | Kind |
|---|---|---|---|
| 18168018.2 | Apr 2018 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2019/059176 | 4/11/2019 | WO | 00 |
