Claims
- 1. A process for the purification of isoserinol to obtain products with a content in organic impurities <0.1% and in inorganic impurities lower than 0.05%, comprising the following steps:
- a) extraction of isoserinol using either esters of acetic acid with (C.sub.1 -C.sub.5) straight or branched alcohols or alcohol solvents of formula Alc--OH wherein Alc is a (C.sub.3 -C.sub.7) straight or branched chain;
- b) formation of the salts of isoserinol with an acid selected from the group consisting of: oxalic acid, an X--Ph--COOH acid, wherein X is a substituent at the phenyl ring Ph such as H, Cl, NO.sub.2, Br and (C.sub.1 -C.sub.4) straight or branched alkyl, or p-toluenesulfonic acid;
- c) crystallization of the salt formed in step b), using alcohol solvents of formula R--OH, wherein R is a (C.sub.1 -C.sub.6) straight or branched alkyl, or monoalkylether glycols of the class of (C.sub.3 -C.sub.7) alkylcellosolves, with water contents from 0.5% to 60%, depending on the used solvent;
- d) release and purification from the salt by use of ion exchange resins, to give compound of formula (I) as the free base;
- e) purification of the free base by crystallization using alcohols of formula R--OH.
- 2. A process according to claim 1, in which the solvent used in step a) is selected from butyl n-acetate and n-pentanol.
- 3. A process according to claim 1, in which the crystallization solvent in step c) is selected from the group consisting of: methanol, ethanol, n-butanol, 2-butanol, 2-methoxyethanol.
- 4. A process according to claim 1, in which the isoserinol salts are formed with the following acids: ortho-chlorobenzoic acid, meta-nitrobenzoic acid, oxalic acid, para-toluenesulfonic acid.
- 5. A process according to claim 4, in which serinol is removed completely below 0.05% by formation of the salts with ortho-chlorobenzoic acid, meta-nitrobenzoic acid or oxalic acid.
- 6. A process according to claim 5, in which the crystallization of isoserinol acid oxalate is carried out in ethanol.
- 7. A process according to claim 5, in which the crystallization of ortho-chlorobenzoate is carried out in isopropanol.
- 8. A process according to claim 5, in which the crystallization of meta-nitrobenzoate is carried out in ethanol containing 5% water (w/w).
- 9. A process according to claim 1, in which the free base is obtained from these salts by use of cationic resins regenerated in the sodium or acidic form.
- 10. A process according to claim 6, in which the resins are selected from the group consisting of: C 20 MB, Amberlite.sup.(R) IR 120, Amberjet.sup.(R) 1200, C 100 E, C 350 MB.
- 11. A process according to claim 6, in which isoserinol is recovered by displacement from the resin with aqueous ammonia.
- 12. A process according to claim 6, in which the progress of the elution of isoserinol from the resin is monitored by observation of pH and fractionation so as to discard those fractions richer in impurities.
- 13. A process according to claim 1, in which the free base is obtained from these salts by use of strong anionic resins.
- 14. A process according to claim 10, in which the resins are selected from the group consisting of: Amberlite.sup.(R) IRA 420, A 400 Purolite, SA 12 A, SBR-P.
- 15. A process according to claim 1, in which anionic and cationic resins are used in sequence.
- 16. A process according to claim 1, in which the crystallization of the free base is carried out when water content ranges from 0.5% to 5%, in precipitation phase, at a temperature from -15.degree. C. to 0.degree. C., depending on the solvent used.
- 17. A process according to claim 13, in which the crystallization of the free base is carried out in a solvent selected from the group consisting of: n-butanol, 2-butanol, isobutanol and n-pentanol.
- 18. A process for the preparation of isoserinol, with a serinol content lower than 0.05% and inorganic impurities content lower than 0.05%, in case the organic impurities content in the starting product does not exceed 0.3% and the content in the isomer serinol is lower than 0.15%, which process comprises the purification of the free base by crystallization using alcohols of formula R--OH, in which R--OH has the same meanings as in claim 1.
- 19. A process for the purification of isoserinol, comprising the following steps:
- a) extraction of isoserinol using either esters of acetic acid with (C.sub.1 -C.sub.5) straight or branched alcohols or (C.sub.3 -C.sub.7) straight or branched alcohol solvents;
- b) formation of a salt of isoserinol with an acid selected from the group consisting of: oxalic acid, an acid of formula X--Ph--COOH, wherein X is a substituent at the phenyl ring Ph such as hydrogen, Cl, NO.sub.2, Br and (C.sub.1 -C.sub.4) straight or branched alkyl, or p-toluenesulfonic acid;
- c) crystallization of the salt obtained in step b) from a solvent selected from an R--OH alcohol, wherein R is a (C.sub.1 -C.sub.6) straight or branched alkyl, or a monoalkylether glycol of the class of (C.sub.3 -C.sub.7) alkylcellosolves, said solvent having a water content from 0.5 to 60%;
- d) release and purification from the salt by elution through ion exchange resins to give isoserinol as the free base;
- e) purification of the free base by crystallization from an alcohol as defined in step c).
- 20. A process according to claim 19, wherein the extraction temperature in step a) ranges from 20 to 50.degree. C.
- 21. A process according to claim 19, wherein the crystallization solvent of step c) is selected from 2-methoxyethanol, ethanol, n-butanol, 2-butanol and methanol.
- 22. A process according to claim 19, wherein the salt from step c) is selected from oxalate, o-chlorobenzoate and m-nitrobenzoate.
- 23. A process according to claim 22, wherein the salt is acid oxalate, the water content ranges from 0 to 30% and the solvent to product ratio ranges from 0.5:1 to 6:1 parts by weight.
- 24. A process according to claim 22, wherein the salt is selected from chlorobenzoate and nitrobenzoate, the water content ranges from 0 to 30%, the solvent to product ratio ranges from 1:0.5 to 1:5 parts by weight and the base is released by elution through regenerated sulfonic resins.
- 25. A process according to claim 22, wherein the salt is para-toluenesolfonate, the water content ranges from 0 to 30%, the solvent to product ratio ranges from 1 to 5 parts by weight and the base is released by elution through strong anionic resins regenerated in the free base or the chloride forms.
- 26. A process according to claim 19, wherein the resin used in step d) is selected from DUOLITE C20 MB, IR 120, AMBERJET 1200, PUROLITE C100 e, PUROLITE A400, AMBERLITE IRA 420, PUROLITE A400.
- 27. A process according to claim 19, wherein isoserinol is displaced from the resin by means of aqueous ammonia.
- 28. A process according to claim 27, wherein 4.7% aqueous ammonia is used.
- 29. A process according to claim 19 and, wherein the anionic and cationic resins are in sequence.
- 30. A process according to claim 19, wherein the crystallization alcohol of step e) has a water content from 0.5 to 5%.
- 31. A process according to claim 19 wherein the crystallization alcohol is selected from n-butanol, 2-butanol, isobutanol and n-pentanol.
- 32. A process for the purification of isoserinol, comprising the crystallization of the free base from an R--OH alcohol, wherein R is a (C.sub.1 -C.sub.6) straight or branched alkyl, said alcohol having a water content from 0.5 to 5%.
- 33. A process for the purification of isoserinol, in particular from its isomer serinol, comprising the following steps:
- a) formation of a salt of isoserinol with an acid selected from the group consisting of: oxalic acid, an acid of formula X--Ph--COOH, wherein X is a substituent at the phenyl ring Ph such as H, Cl, NO.sub.2, Br and a (C.sub.1 -C.sub.4) straight or branched alkyl, or p-toluenesulfonic acid;
- b) crystallization of the salt formed in step b) from a solvent selected from the group consisting of an R--OH alcohol, wherein R is a (C.sub.1 -C.sub.6) straight or branched alkyl, or monoalkylether glycols of the class of (C.sub.3 -C.sub.7) alkylcellosolves, with water contents from 0.5% to 60%;
- c) release and purification from the salt by use of ion exchange resins, to give isoserinol as the free base;
- d) purification of the free base by crystallization using alcohols of formula R--OH.
- 34. A process according to claim 33, wherein the crystallization solvent of step b) is n-butanol.
Priority Claims (1)
Number |
Date |
Country |
Kind |
MI97A0782 |
Apr 1997 |
ITX |
|
Parent Case Info
This application is a 371 of PCT/EP98/01874 filed Apr. 1, 1998.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP98/01874 |
4/1/1998 |
|
|
10/4/1999 |
10/4/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/45247 |
10/15/1998 |
|
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 470 004 A1 |
Feb 1992 |
EPX |