Claims
- 1. A process for the optical resolution of racemic (.+-.) (2RS,3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(methoxyphenyl) propionic acid (II) with half mole equivalent of optical resolving agent (+).alpha.-methylbenzylamine (III) and half mole equivalent of an alkali in the presence of a polar solvent at a temperature in the range of 70-80.degree. C.,to form a precipitate of (+).alpha.-methylbenzylamine salt of (2S,3S) propionic acid (I) with (-) (2R,3R) propionic acid remaining in solution, and then converting the precipitate to the free acid (+) (2S, 3S)-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid (I) giving substantially optically pure form of said propionic acid (I).
- 2. The process according to claim 1 wherein the alkali is selected from the group consisting of KOH, NaOH, LiOH, NH.sub.4 OH, and mixtures thereof.
- 3. The process according to claim 1 wherein the polar solvent consists of water.
- 4. The process according to claim 1, wherein the optical resolving agent (+).alpha.-methylbenzylamine (III) and alkali are added simultaneously with stirring to the racemic (.+-.) (2RS,3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(methoxyphenyl) propionic acid (II) at a temperature in the range of 70-80.degree. C.
- 5. The process according to claim 1, wherein after addition of optically resolving agent (+).alpha.-methylbenzylamine (III) and the alkali, the reaction mixture is stirred further for a period in the range of 5 to 6 hrs at room temperature.
- 6. The process according to claim 1, wherein the substantially optically pure propionic acid (I) is purified by recrystallization using a solvent selected from the group consisting of water, methanol, ethanol, acetone, alkanol-water and mixtures thereof.
- 7. The process according to claim 1, wherein the polar solvent has at least one component selected from the group consisting of water, methanol, ethanol, acetone, benzene, and ethylacetate.
- 8. The process according to claim 3, wherein the optical resolving agent (+).alpha.-methylbenzylamine (III) and alkali are added simultaneously with stirring to the racemic (.+-.) (2RS,3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(methoxyphenyl) propionic acid(II) at a temperature in the range of 70-80.degree. C.
- 9. The process according to claim 3, wherein after addition of optically pure resolving agent (+).alpha.-methylbenzylamine (III) and the alkali, the reaction mixture is stirred further for a period in the range of 5 to 6 hrs at room temperature.
- 10. The process according to claim 3, wherein the substantially optically pure propionic acid (I) is purified by recrystallization using a solvent selected from the group consisting of water, methanol, ethanol, acetone, alkanol-water and mixtures thereof.
- 11. The process according to claim 1, wherein the conversion of the precipitate is by using hydrochloric acid (HCl).
- 12. The process according to claim 11 wherein the conversion includes suspension of the precipitate in distilled water, treatment with sodium hydroxide (NaOH) and neutralization with hydrochloric acid (HCl).
- 13. The process according to claim 3 wherein the conversion of the precipitate is by using hydrochloric acid (HCl).
- 14. The process according to claim 13 wherein the conversion includes suspension of the precipitate in distilled water, treatment with sodium hydroxide (NaOH) and neutralization with hydrochloric acid (HCl).
- 15. The process according to claim 1, wherein the optical resolving agent (+).alpha.-methylbenzylamine (III) and alkali are added in alternating portions while stirring to the racemic (.+-.) (2RS, 3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(methoxyphenyl) propionic acid (II) at a temperature in the range of 70-80.degree. C.
- 16. A process for the optical resolution of racemic (.+-.) (2RS,3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(methoxyphenyl) propionic acid (II) with half mole equivalent of optical resolving agent (+).alpha.-methylbenzylamine (III) and half mole equivalent of an alkali in the presence of water at a temperature in the range of 70-80.degree. C., to form a precipitate of (+).alpha.-methylbenzylamine salt of (2S,3S) propionic acid (I) with (-) (2R,3R) propionic acid remaining in solution, and then converting the precipitate to the free acid (+) (2S,3S)-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionic acid (I) giving substantially optically pure form of said propionic acid (I) wherein the optical resolving agent (+).alpha.-methylbenzylamine (III) and alkali are added in alternating portions while stirring to the racemic (.+-.) (2RS,3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(methoxyphenyl) propionic acid (II).
Parent Case Info
This application is a continuation of application Ser. No. 08/379,133, filed Jan. 27, 1995 now abandoned.
US Referenced Citations (6)
Non-Patent Literature Citations (3)
Entry |
CA 106: 33134g (1986). |
E.J.Corey and John Mann, A New Stereocontrolled Synthesis of Prostaglandins via Prostaglandin A.sub.2, Journal of the American Chemical Society, Oct. 3, 1973, pp. 6832-6833. |
Merck Research Laboratories, The Merck Index, 1996, p. 1031. |
Continuations (1)
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Number |
Date |
Country |
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379133 |
Jan 1995 |
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