Methods for producing nateglinide crystals
AssigneeAjinomoto Co., Inc.
InventorsDaisuke Takahashi, Seiichi Nishi, Satoji Takahashi
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Abstract
There is provided methods for producing nateglinide crystals, which comprises the steps of adding an acid(s) to a reaction mixture containing nateglinide to make it acidic, the reaction mixture being obtained by reacting trans-4-isopropylcyclohexylcarbonyl chloride with D-phenylalanine in a mixed solvent of ketone solvent and water in the presence of an alkali; and then adjusting the temperature of the mixture to 58° C. to 72° C. and the concentration of ketone solvent to more than 8 wt % and less than 22 wt % to conduct precipitation of nateglinide crystals. This producing method is the industrially beneficial methods for crystallization of nateglinide.
Claims12
A method for producing nateglinide crystals, which comprises:
- (a) mixing hydrochloric acid and, optionally, one or more acids with a first reaction mixture, said first reaction mixture comprising nateglinide, to obtain a second reaction mixture which is acidic, wherein said first reaction mixture is obtained by reacting trans-4-isopropylcyclohexylcarbonyl chloride with D-phenylalanine in a mixed solvent comprising acetone and water in the presence of potassium hydroxide;
- (b) adjusting the temperature of said second reaction mixture to 63° C. to 65° C. and the concentration of acetone to more than 8 wt % and less than 22 wt %, maintaining the second reaction mixture at 63° C. to 65° C., and cooling the second reaction mixture to effect precipitation of nateglinide crystals;
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- (c) isolating the nateglinide crystals.
Dependencies are inferred from the claim text.