GB1377336A - Method of separating rho- di-2-chloroethyl- -amino- de -phenylalanine into optical isomers - Google Patents

Abstract

1377336 Resolution of p-[di-(2-chloroethyl)- amino]-phenylalanine INSTITUT BIOKHIMII AKADEMII NAUK LITOVSKOI SSR and INSTITUTELEMENTOORGANICHESKIKH SOEDINENY AKADEMII NAUK SSSR 3 March 1973 10418/73 Heading C2C A method of separating p-[di-(2-chloroethyl)- amino]-DL-phenylalanine into optical isomers, residing in that p-[di-(2-chloroethyl)amino]- DL-phenylalanine is treated with formic acid and acetic anhydride; the thus-formed N- formyl - p - [di - (2 - chloroethyl)amino] - DL- phenylalanine is isolated from the reaction mixture and dissolved in ethanol at 50-78‹ C.; the thus-prepared solution is treated with a solution of brucine in ethanol at 50-78‹ C. with the stoichiometric relationship between N- formyl - p - [di - (2 - chloroethyl)amino] - DL- phenylalanine and brucine or with a slight excess of the latter; the resultant solution is cooled down to room temperature, with the result that the brucine salt of N-formyl-p-[di- (2 - chloroethyl)amino] - D - phenylalanine is precipitated, while remaining in the mother liquor is N-formyl-p-[di-(2-chloroethyl)amino]- L-phenylalanine; the latter, after having been treated with a solution of sodium ethylate in ethanol, is isolated from said mother liquor as a sodium salt; said sodium salt is dissolved in water and treated with a 0À05-0À5N hydrochloric acid solution to obtain N-formyl-p-[di- (2 - chloroethyl)amino] - L - phenylalanine as precipitate; said precipitate is dissolved in a 4-5N hydrochloric acid solution while being heated to 60-80‹ C., whereupon p-[di-(2- chloroethyl)amino] - L - phenylalanine is isolated from the solution; aforesaid brucine salt of N - formyl - p - [di - (2 - chloroethyl)- amino] - D - phenylalanine is dissolved in ethanol at 50-78‹ C., whereupon said salt is converted, by being affected with an ethanol solution of sodium ethylate, into a sodium salt of N - formyl - p - [di - (2 - chloroethyl)amino] - D- phenylalanine which then precipitates; the thus-formed precipitate is separated from the mother liquor, dissolved in water and treated with a 0À05-0À5N hydrochloric acid solution to obtaint the precipitate of N-formyl-p-[di-(2- chloroethyl)amino] - D - phenylalanine; said precipitate is dissolved in a 4-5N hydrochloric acid solution, while being heated to 60-80‹ C., whereupon p - [di - (2 - chloroethyl)amino] - D phenylalanine is isolated from the solution.