Process for purifying n2-(1(s)-ethoxycarbonyl-3-phenylpropyl)-n6-thifluoroacetyl-l-lysine

#The present invention relates to a process for purifying N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine of the formula (1):

#N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine is a compound very useful as intermediates for the production of drugs and medicines, particularly as an intermediate for the production of antihypertensive agent (angiotensin converting enzyme inhibitor) lysinopril.

#As a process of the synthesis of N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine are hitherto known (a) a process wherein after conducting a Michael addition reaction of N6-trifluoroacetyl-L-lysine to ethyl β-benzoylacrylate, carbonyl group in the benzoyl portion is converted into methylene group by catalytic reduction (JP-B-4-4308), (b) a process wherein ethyl 2-oxy-4-phenylbutyrate and N6-trifluoroacetyl-L-lysine are subjected to reductive amination (CN-B-1053437), and the like.

#FIG. 1 is a powder X-ray diffraction pattern of crystals of I form of N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine;

#FIG. 2 is a powder X-ray diffraction pattern of crystals of II form of N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine;

#FIG. 3 is a powder X-ray diffraction pattern of crystals of III form of N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine;

#The purification process of the present invention comprises crystallizing N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine from a solvent comprising a water-soluble non-protic organic solvent.

#In the present invention, in order to obtain N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine with high quality, namely high purity and good physical properties of crystals, in a high yield and a high productivity from N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine contaminated with impurities, the crystallization is carried out from a water-soluble non-protic organic solvent alone or a solvent containing a water-soluble non-protic organic solvent.

#The water-soluble non-protic organic solvent is not particularly limited. Examples thereof are, for instance, acetonitrile, acetone, methyl ethyl ketone, tetrahydrofuran, dioxane, and the like. Of these, acetonitrile is the most preferable.