Herstellung von Cephalosporinverbindungen

摘要

1,269,697. Silylated cephalosporin derivatives. ELI LILLY & CO. 22 Aug., 1969 [23 Aug., 1968], No. 42066/69. Heading C2A. [Also in Division C3] Novel silylated cephalosporin derivatives of Formula VI wherein R11 is hydrogen or acetoxy, and R1, R2 and R3 are each hydrogen or a C 1 to C 8 hydrocarbon radical free from aliphatic unsaturation, with not more than two of R1 , R2 and R3 bonded to the same silicon atom being hydrogen, and R10 is hydrogen or the group: are prepared by reacting 7-aminocephalosporanic acid or 7-amino-desacetoxycephalosporanic acid or a salt thereof, with a mono- or bissilylamide of one of the Formulµ I to V wherein R1, R2 and R3 are as defined above; R5 and R9 are each hydrogen or C 1 to C 8 hydrocarbon free from aliphatic unsaturation, R8 is C 1 to C 8 hydrocarbon free from aliphatic unsaturation; each of R4, R6 and R7 is hydrogen or C 1 to C 8 hydrocarbon free from aliphatic unsaturation, or R6 and R7 together with the common nitrogen complete a heterocyclic ring containing 5 to 6 ring-forming atoms, one of which can be oxygen para to the nitrogen, or 4 to 6 ring-forming carbons provided that R6 and R7 together contain not more than 18 carbons and that if R6 is alkyl with tert. carbon bonded to the nitrogen then R7 is hydrogen; or R4 and R6 together with the attached nitrogens and the carbonyl group form a heterocyclic ring containing 5 to 6 ring-forming atoms and 2 to 3 methylene ring-forming carbon atoms; and Y is a C 3 to C 18 alkylene group with a 3 to 5 carbon chain between the nitrogen and the carbonyl group to which Y is bonded, the reaction being effected in an anhydrous aprotic solvent at - 25‹ to +50‹ C. The invention includes a composition comprising (a) a compound of Formula VI above, (b) a silylamide of one of Formulµ I to V above and (c) an anhydrous solvent for (a) and (b) of which the molecules do not contain Zerewitinoff hydrogen. The silylated cephalosporins may be converted to known antibiotically active cephalosporins by reacting with an appropriate acylating agent to give the corresponding N-acylated silyl ester which is treated with a C 1 to C 6 alkanol to give the required cephalosporin which is recovered from the solution preferably as the Na or K salt. Cephalothin, cephaloglycin and cephalexin are prepared in this way.