Patent ID: 8940929
Filing Date: 2015-01-27
Classification: C07B,C07C

Abstract:
1. A method for preparation high-optical purity N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine, comprising: (1) adding crude N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine to an organic solvent at a mass-to-volume ratio of 1:1˜50, at the temperature of −20 to 50° C., adding an organic acid to the reaction system, and then carrying out a reaction for 5 to 24 hours with stirring, so that a salt is formed and precipitated as a solid; filtering the reaction mixture, and concentrating the filtrate to dryness under a reduced pressure at a temperature lower than 40° C., to obtain a mother concentrate, wherein the molar ratio of the 1S-isomer to the 1R-isomer of the crude N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine is 80:20; and the molar ratio of the organic acid to the crude N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine is 0.5 to 1.5:1; (2) adding the solid or the mother concentrate obtained in Step (1) to deionized water at a weight-to-volume ratio of 1:1˜25, at a temperature of −20˜50° C., adding an inorganic or an organic base for basification, and adjusting the pH value to 4.0˜6.0, cooling the reaction mixture to 0˜5° C., and stirring the reaction solution for 3 hours, then after filtering, washing, and drying, the high-optical purity N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine is obtained with a molar ratio of the 1S-isomer to the 1R-isomer to be equal to or greater than 99:1.