Claims
- 1. A process for producing a compound of formula 31
- 2. A process according to claim 1, wherein in Reaction I a chiral catalyst is used, wherein the chiral catalyst is selected from the group consisting of a chiral auxiliary reagent, a Lewis acid and a Brønsted base, or a combination thereof.
- 3. A process according to claim 2, wherein the chiral auxiliary reagent is diether (S, S)-1,2-dimethoxy-1,2-diphenylethane.
- 4. A process according to claim 1, wherein the compound of formula 31 is hydrolyzed with a base.
- 5 A process according to claim 4, wherein the base is NaOH.
- 6. A process according to claim 1, wherein the compound of formula 31 is further purified.
- 7. A process according to claim 6, wherein the compound of formula 31 is purified by column chromatography.
- 8. A process according to claim 1, wherein the compound R4SH is used as a lithium thiolate or is converted into lithium thiolate during or before reaction I.
- 9. A process according to claim 8, wherein butyllithium (BuLi) is used before reaction I to convert the compound of the formula R4SH into lithium thiolate.
- 10. A process according to claim 9, wherein an equivalent ratio of BuLi:R4SH of between 1:5 and 1:20 is used.
- 11. A process according to claim 9, wherein the equivalent ratio of BuLi:R4SH is 1:10.
- 12. A process according to claim 1, wherein at the beginning of reaction I, the reaction temperature is not higher than 0° C., and over the course of reaction I, the temperature is adjusted to room temperature.
- 13. A process according to claim 1, wherein at the beginning of reaction I, the reaction temperature is between about −70 and about −80° C.
- 14. A process according to claim 1, wherein at the beginning of reaction I, the reaction temperature is about −78° C.
- 15. A process according to claim 1, wherein at the beginning of reaction I, the reaction temperature is not higher than 0° C., and over the course of reaction I, the temperature is adjusted to between about −20° C. and about −10° C.
- 16. A process according to claim 15, wherein at the beginning of reaction I, the reaction temperature is at between about −30 and about −20° C., and over the course of reaction I, the temperature is adjusted to between about −20° C. and about −10° C.
- 17. A process according to claim 16, wherein at the beginning of reaction I, the reaction temperature is at about −25° C., and over the course of reaction I, the temperature is adjusted to −15° C.
- 18. A process according to claim 1, wherein reaction I proceeds in an organic solvent.
- 19. A process according to claim 1, wherein reaction I proceeds in a nonpolar solvent.
- 20. A process according to claim 1, wherein the organic solvent is toluene, ether, tetrahydrofuran (THF) or dichloromethane (DCM).
- 21. A process according to claim 1, wherein diastereomers of the compound of formula 31 are separated after reaction I.
- 22. A process according to claim 21, wherein diastereomers are separated by preparative HPLC or crystallization.
- 23. A process according to claim 22, wherein diastereomers are separated by crystallization using pentane/ethanol (10:1) as solvent and cooling.
- 24. A process according to claim 21, wherein enantiomers of the compound of formula 31 are separated prior to the separation of the diastereomers.
- 25. A process according to claim 1, wherein R1 is C1-6 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; and R2 is C2-9 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted.
- 26. A process according to claim 25, wherein R1 is C1-2 alkyl, mono- or polysubstituted or unsubstituted, and R2 is C2-9 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted.
- 27. A process according to claim 25, wherein R1 is methyl or ethyl.
- 28. A process according to claim 25, wherein R2 is C2-7 alkyl.
- 29. A process according to claim 25, wherein R2 is ethyl, propyl, n-propyl, i-propyl, butyl, n-butyl, i-butyl, tert.-butyl, pentyl, hexyl or heptyl.
- 30. A process according to claim 1, wherein R1 is methyl and R2 is n-butyl.
- 31. A process according to claim 1, wherein R3 is C1-3 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted.
- 32. A process according to claim 31, wherein R3 is methyl or ethyl.
- 33. A process according to claim 1, wherein R4 is C1-6 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; phenyl or thiophenyl, unsubstituted or monosubstituted; or unsubstituted or monosubstituted phenyl attached via CH3.
- 34. A process according to claim 33, wherein R4 is phenyl or thiophenyl monosubstituted with OCH3, CH3, OH, SH, CF3, F, Cl, Br or I.
- 35. A process according to claim 33, wherein R4 is phenyl monosubstituted with OCH3, CH3, OH, SH, CF3, F, Cl, Br or I, attached via CH3.
- 36. A process according to claim 33, wherein R4 is saturated, unbranched and unsubstituted, C1-6 alkyl.
- 37. A process according to claim 34, wherein R4 is methyl, ethyl, propyl, n-propyl, i-propyl, butyl, n-butyl, i-butyl, tert.-butyl, pentyl or hexyl.
- 38. A process according to claim 33, wherein R4 is methyl, ethyl, or benzyl unsubstituted or monosubstituted with OCH3, CH3, OH, SH, CF3, F, Cl, Br or I.
- 39. A process according to claim 8, wherein the thiolate is used stoichiometrically, and an adduct of the thiolate to the compound of Formula 30 is formed, and wherein chlorotrimethylsilane (TMSCl) is used to scavenge the adduct, forming an enol ether.
- 40. A process according to claim 39, wherein the enol ether is further protonated by a chiral proton donor R*-H.
- 41. A process according to claim 1, wherein the compound of formula 30 is modified before reaction I with a sterically demanding group.
- 42. A process according to claim 41, wherein the sterically demanding group is t-Butyldimethylsiloxy (TBDMS).
- 43. A process according to claim 1, wherein the compound of formula 31 is 3-ethylsulfanyl-2-formylamino-3-methyloctanoic acid ethyl ester or 3-benzylsulfanyl-2-formylamino-3-methyloctanoic acid ethyl ester, the compound of formula 30 is 2-formylamino-3-methyl-2-octenoic acid ethyl ester, and R4SH is ethyl mercaptan or benzyl mercaptan.
- 44. A compound of formula 31
- 45. A compound according to claim 44, in the form of a salt thereof with a cation or a base, or a salt with a anion or an acid.
- 46. A compound according to claim 44, wherein R1 is C1-6 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; and R2 is C2-9 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted.
- 47. A compound according to claim 46, wherein R1 is C1-2 alkyl, mono- or polysubstituted or unsubstituted, and R2 is C2-9 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted.
- 48. A compound according to claim 46, wherein R1 is methyl or ethyl.
- 49. A compound according to claim 46, wherein R2 is C2-7 alkyl.
- 50. A compound according to claim 46, wherein R2 is ethyl, propyl, n-propyl, i-propyl, butyl, n-butyl, i-butyl, tert.-butyl, pentyl, hexyl or heptyl.
- 51. A compound according to claim 44, wherein R1 is methyl and R2 is n-butyl.
- 52. A compound according to claim 44, wherein R3 is C1-3 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted.
- 53. A compound according to claim 52, wherein R3 is methyl or ethyl.
- 54. A compound according to claim 44, wherein R4 is C1-6 alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; phenyl or thiophenyl, unsubstituted or mono substituted; or unsubstituted or mono substituted phenyl attached via CH3.
- 55. A compound according to claim 54, wherein R4 is phenyl or thiophenyl monosubstituted with OCH3, CH3, OH, SH, CF3, F, Cl, Br or I.
- 56. A compound according to claim 54, wherein R4 is phenyl monosubstituted with OCH3, CH3, OH, SH, CF3, F, Cl, Br or I, attached via CH3.
- 57. A compound according to claim 54, wherein R4 is saturated, unbranched and unsubstituted, C1-6 alkyl.
- 58. A compound according to claim 55, wherein R4 is methyl, ethyl, propyl, n-propyl, i-propyl, butyl, n-butyl, i-butyl, tert.-butyl, pentyl or hexyl.
- 59. A compound according to claim 54, wherein R4 is methyl, ethyl, or benzyl unsubstituted or monosubstituted with OCH3, CH3, OH, SH, CF3, F, Cl, Br or I.
- 60. A compound according to claim 1, which is 3-ethylsulfanyl-2-formylamino-3-methyloctanoic acid ethyl ester or 3-benzylsulfanyl-2-formylamino-3-methyloctanoic acid ethyl ester.
Priority Claims (1)
Number |
Date |
Country |
Kind |
100 45 832.7 |
Sep 2000 |
DE |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of International Patent Application No. PCT/EP01/10626, filed Sep. 14, 2001, designating the United States of America and published in German as WO 02/22569, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany Patent Application No. 100 45 832.7, filed Sep. 14, 2000.
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/EP01/10626 |
Sep 2001 |
US |
Child |
10387870 |
Mar 2003 |
US |