| 摘要 |
Process for the preparation of / D- alpha -amino-p- hydroxyphenylacetamido/ groups containing penicillanic acid and cephalosporanic acid derivatives, comprising the acylation of a compounds of the formulae: <CHEM> wherein R1, R2 and R3 represent the same or a different group and may be selected from a lower alkyl, benzyl, cycloalkyl or phenyl-group and preferably lower alkyl and more preferably a methyl group and wherein X represents a residue selected from the group consisting of hydrogen, acetoxy or a fivemembered heterocyclic thio residue, containing heteroatoms selected from nitrogen, oxygen and/or sulphur and optionally substituted by lower alkyl and wherein an eventually present -NH- radical has optionally been silylated, which compound is previously prepared by the reaction of 6-aminopenicillanic acid or 7-aminocephalosporanic acid or its 3-methyl modifications with at least one equivalent and preferably about 2 with respect to 6-APA, 7-ACA or 7-ADCA and about 3 equivalents with respect to other 3-methyl modifications of 7-ACA of a tri(lower)alkyl silyl groups supplying agent in a dry inert, water insoluble solvent, such as methylene chloride, by rapid mixing of a pre-cooled solution of the compound of formula I-IV with a pre-cooled reaction mixture of at least an equimolar amount of a compound of the formula <CHEM> wherein R4 represents lower alkyl and preferably methyl, R5 represents hydrogen or lower alkyl and preferably methyl, R6 represents lower alkoxy and preferably methoxy and R7 represents lower alkoxy and preferably methoxy, previously prepared from the corresponding Dane salt and an acid chloride under anhydrous conditions in the presence of a tertiary amine as catalyst, such as N-methylmorpholine in a dry, inert, water insoluble, organic solvent such as methylene chloride mixed with a cosolvent or methyl isobutylketone or tetrahydrofuran optionally mixed with a cosolvent, and the continuation of the reaction at a temperature of -10 DEG C or lower and preferably from 20 DEG C to 30 DEG C whereafter the desired compound is recovered by usual methods. |
