Verfahren zur Herstellung von Aminopenicillinen

摘要

1,254,194. Preparation of monosilylated hydrohalide salts of aminopenicillins and the corresponding aminopenicillins. AMERICAN HOME PRODUCTS CORP. 2 April, 1969 [5 Dec., 1968], No. 17211/69. Heading C2A. Monosilylated hydrohalide salts of penicillins having the general formula wherein, when R and R1 are separate, R is hydrogen and R1 is phenyl which may be substituted, or when R and R1 are joined they complete an indane or cycloalkyl ring system having from 4 to 9 carbon atoms which may be substituted; and X is Cl or Br, are prepared by (a) preparing a mixture containing one molar proportion of 6-aminopenicillanic acid and from 0À6 to 0À8 molar proportion of hexamethyldisilazane, in methylene chloride; (b) heating the mixture at reflux to form mono-(trimethylsilyl)-6-aminopenicillanic acid and ammonia; and (c) treating the resulting mono-(trimethylsilyl)-6-aminopenicillanic acid with about one molar proportion of a weak base and about one molar proportion of an organic acid halide hydrohalide having the formula The corresponding penicillin hydrohalide may be formed by removing the silyl group by solvolysis and the aminopenicillin may be isolated, e.g. by adjustment of the isoelectric point with alkali. The weak base may be N,N- dimethylaniline, quinoline or pyridine and the organic acid halide hydrohalide may be D(-)- phenylglycyl-, 1-amino-1-cyclohexane-carboxylic acid-, 2-amino-2-carboxyindane- or 1-amino- 1-carboxyindane-chloride hydrochloride. The phenyl, cycloalkyl and indanyl rings may be substituted by C 1-3 alkyl, C 1-3 alkoxy, Cl, Br, F, trihalomethyl, nitro or amino. Comparative examples relate to the above process wherein chloroform and benzene are substituted for the methylene chloride.