Purification method of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine

1. A purification method of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine represented by the formula (1)

which comprises crystallizing impurity-contaminated N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine from a mixed solvent of alcohol and water in a volume ratio of alcohol/water being 1/1 to 20/1 to remove a contaminating impurity into a mother liquor and give crystals of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine,

said alcohol being a monohydric alcohol of 1 to 12 carbon atoms.

2. The purification method according to claim 1

wherein the contaminating impurity is at least one compound selected from the group consisting of N-(1(R)-ethoxycarbonyl-3-phenylpropyl)-L-alanine represented by the following formula (2),

N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-D-alanine represented by the following formula (3),

N-(1(R)-ethoxycarbonyl-3-phenylpropyl)-D-alanine represented by the following formula (4),

N-(1(S)-ethoxycarbonyl-3-cyclohexylpropyl)-L-alanine represented by the following formula (5),

N-(1(S)-carboxy-3-phenylpropyl)-L-alanine represented by the following formula (6),

N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine ester of the following formula (7)

in the formula, R represents an alkyl group or an aralkyl group,

and ethyl phenylbutyrate.

3. The purification method according to claim 1 wherein the crystallization is carried out under forced fluidity with a condition of not less than 0.1 kW/m3.

4. The purification method according to claim 1 wherein in the crystallization is carried out at a temperature of not lower than 20° C.

5. The purification method according to claim 1 wherein the crystallization is carried out at a crystallizing speed of not more than 50% of a total crystal output/hour.

6. The purification method according to claim 1 wherein the crystallization is carried out at pH 3 to 6.

7. The purification method according to claim 1 wherein the crystallization is carried out by at least one of crystallization by cooling and crystallization by concentration.

8. The purification method according to claim 7 wherein the crystallization is carried out by crystallization by cooling.

9. The purification method according to claim 8 wherein the cooling speed for the crystallization by cooling is not more than 40° C./hour.

10. The purification method to claim 1 wherein the alcohol is a monohydric alcohol of 1 to 8 carbon atoms.

11. The purification method according to claim 10 wherein the alcohol is a monohydric alcohol of 1 to 4 carbon atoms.

12. The purification method according to claim 11 wherein the alcohol is ethanol.

13. The purification method according to claim 12

wherein the ethanol is denatured with at least one denaturing agent selected from the group consisting of ethyl acetate, methyl isobutyl ketone, aliphatic hydrocarbons and aromatic hydrocarbons.

14. The purification method according to claim 1 wherein a treatment with an active charcoal is carried out prior to the crystallization.

15. The purification method according to claim 2 where in the crystallization is carried out under forced fluidity with a condition of not less than 0.1 kW/m3.

16. The purification method according to claim 3 where in the crystallization is carried out at a temperature of not lower than 20° C.

17. The purification method according to claim 4 wherein the crystallization is carried out at a crystallizing speed of not more than 50% of a total crystal output/hour.

18. The purification method according to claim 5 wherein the crystallization is carried out at pH 3 to 6.

19. The purification method according to claim 6 wherein the crystallization is carried out by at least one of crystallization by cooling and crystallization by concentration.

20. The purification method according to claim 1 , wherein the volume ratio of alcohol/water is 1.5 to 20.

21. The purification method according to claim 20 , wherein the volume ratio of alcohol/water is 2 to 20.

22. The purification method according to claim 1 , which is a method for reducing N-1(S)-ethoxycarbonyl-3-cyclohexylpropyl-L-alanine content to not more than 0.47% through a crystallization process.