Claims
- 1. A process for the preparation of the hydrohalide of .alpha.-L-aspartyl-L-phenylalanine methyl ester, comprising esterifying .alpha.-L-aspartyl-L-phenylalanine in the presence of an alkali metal halide or alkaline earth metal halide in a medium consisting of sulfuric acid, water and methanol, the amount of the alkali metal halide or alkaline earth metal halide being at least 1 equivalent relative to the .alpha.-L-aspartyl-L-phenylalanine, thereby allowing the resulting .alpha.-L-aspartyl-L-phenylalanine methyl ester to precipitae as its corresponding hydrohalide, and then isolating the hydrohalide.
- 2. The process as claimed in claim 1, wherein the concentration of the sulfuric acid is 5-50 wt. % based on the sum of the sulfuric acid and water in the reaction system, the concentration of the methanol is 3-35 wt. % based on the sum of the methanol and water in the reaction system, and the amounts of the sulfuric acid and methanol are each at least 1 equivalent relative to the .alpha.-L-aspartyl-L-phenylalanine.
- 3. The process as claimed in claim 1, wherein an alkali metal chloride or alkaline earth metal chloride is used.
- 4. The process as claimed in claim 1, wherein magnesium chloride is used.
- 5. The process as claimed in claim 1, wherein the esterification is conducted at 0.degree.-60.degree. C.
- 6. The process as claimed in claim 1, wherein the .alpha.-L-aspartyl-L-phenyl alanine is that formed in situ by treating an N-protected-.alpha.-L-aspartyl-L-phenylalanine in an aqueous solution of sulfuric acid or a methanol-containing aqueous solution of sulfuric acid.
- 7. The process as claimed in claim 6, wherein the concentration of the sulfuric acid is 5-50 wt. % based on the sum of the sulfuric acid and water in the reaction system, the concentration of the methanol is 3-35 wt. % based on the sum of the methanol and water in the reaction system, and the amounts of the sulfuric acid and methanol are each at least 1 equivalent relative to the N-protected-.alpha.-L-aspartyl-L-phenylalanine.
- 8. The process as claimed in claim 6, wherein an alkali metal chloride or alkaline earth metal chloride is used.
- 9. The process as claimed in claim 6, wherein magnesium chloride is used.
- 10. The process as claimed in claim 6, wherein the esterification is conducted at 0.degree.-60.degree. C.
- 11. A process for the preparation of .alpha.-L-aspartyl-L-phenylalanine methyl ester comprising esterifying .alpha.-L-aspartyl-L-phenylalanine in the presence of an alkali metal halide or alkaline earth metal halide in a medium composed of sulfuric acid, water and methanol, the amount of the alkali metal halide or alkaline earth metal halide being at least 1 equivalent relative to the .alpha.-L-aspartyl-L-phenylalanine, thereby to allow the resulting .alpha.-L-aspartyl-L-phenylalanine methyl ester to precipitate as its corresponding hydrohalide, then isolating the hydrohalide, and neutralizing the hydrohalide to provide the methyl ester.
- 12. The process as claimed in claim 11 wherein the concentration of the sulfuric acid is 5 to 50 weight percent based on the sum of the sulfuric acid and water in the reaction system, the concentration of the methanol is 3 to 35 weight percent based on the sum of the methanol and water in the reaction system, and the amounts of the sulfuric acid and methanol are each at least 1 equivalent relative to the .alpha.-L-aspartyl-L-phenylalanine.
- 13. The process as claimed in claim 11 wherein an alkali metal chloride or alkaline earth metal chloride is used.
- 14. The process as claimed in claim 11 wherein magnesium chloride is used.
- 15. The process as claimed in claim 11 wherein the esterification is conducted at 0.degree. to 60.degree. C.
- 16. The process as claimed in claim 1, wherein the .alpha.-L-aspartyl-L-phenylalanine is that formed in situ by treating an N-protected-.alpha.-L-aspartyl-L-phenylalanine in an aqueous solution of sulfuric acid or a methanol-containing aqueous solution of sulfuric acid.
- 17. The process as claimed in claim 16 wherein the concentration of the sulfuric acid is 5 to 50 weight percent based on the sum of the sulfuric acid and water in the reaction system, the concentration of the methanol is 3 to 35 weight percent based on the sum of the methanol and water in the reaction system, and the amounts of the sulfuric acid and methanol are each at least 1 equivalent relative to the N-protected-.alpha.-L-aspartyl-L-phenylalanine.
- 18. The process as claimed in claim 16 wherein an alkali metal chloride or alkaline earth metal chloride is used.
- 19. The process as claimed in claim 16 wherein magnesium chloride is used.
- 20. The process as claimed in claim 16 wherein the esterification is conducted at 0.degree. to 60.degree. C.
- 21. The process as claimed in claim 11 wherein the neutralization of the hydrohalide is conducted by contacting the hydrohalide with an aqueous solution of a base selected from the group consisting of a caustic alkali, an alkali carbonate and an alkali bicarbonate.
- 22. The process as claimed in claim 21 wherein the base is sodium carbonate.
- 23. The process as claimed in claim 21 wherein the neutralized aqueous mixture is cooled and the precipitate is filtered out of the neutralized aqueous mixture.
Priority Claims (2)
Number |
Date |
Country |
Kind |
61-288888 |
Dec 1986 |
JPX |
|
61-288889 |
Dec 1986 |
JPX |
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Parent Case Info
This application is a continuation of prior U.S. application Ser. No. 126,729 filing date Nov. 30, 1987, which is now abandoned.
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Continuations (1)
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Number |
Date |
Country |
Parent |
126729 |
Nov 1987 |
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