| 摘要 |
1391271 Preparation of 7-amino-cephalo- Sporins GLAXO LABORATORIES Ltd 24 April 1972 [30 April 1971] 12444/71 Heading C2C A process for the preparation of a 7-aminocephalosporanic acid comprises protecting both of the carboxyl groups of a 7-(4<SP>1</SP>-carboxybutanamido)cephalosporin - 4 - carboxylic acid by forming a double mixed anhydride thereof in an inert organic solvent under substantially anhydrous conditions, contacting the resultant solution with an imide halide-forming compound, commingling the resultant reaction mixture with an imino ether-forming compound, cleaving the reaction product and recovering the 7-aminocephalosporin formed. Suitable agents with which to form mixed anhydrides include acetyl, propionyl or chloroacetyl chloride, halides of benzoic acid or a nitro- or methoxy-benzoic acid. The mixed anhydrides may be formed in the temperature range -50‹ to +40‹ C., preferably -10‹ to +20‹ C. The mixed anhydride formation may be carried out in the presence of an organic tertiary base such as N,N-dimethylaniline or quinoline. The imide halide-forming compound may be phosphorus pentachloride and the imide halide-forming reaction may be carried out at -50‹ to + 50‹ C., preferably -30‹ to + 10‹ C. This reaction may be carried out in the presence of a tertiary base such as N,N-dimethylamine dr quinoline. The imino ether-forming compound may be a C 1 -C 6 alkanol such as methanol or a C 2 -C 4 alkane diol and the imino ether-forming reaction may be carried out in the temperature range -50‹ to + 20‹ C., preferably -50‹ to -10‹ C. The preparation of (6R, 7R)-3-acetoxymethyl- 7 - aminoceph - 3 - em - 4 - carboxylic acid from (6B, 7R) - 3 - acetoxymethyl - 7 - (4<SP>1</SP>- carboxybutanamido)ceph - 3 - em - 4 - carboxylic acid is described. |
