Patent ID: 6414140
Filing Date: 2002-07-02
Classification: C07D

Abstract:
A process for the production of a 3-vinylcephalosporin compound of formula I wherein R1 and R2 may be the same or different and denote hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl wherein Câ€”C bonds are unsaturated, aryl, aralkyl, or heterocyclyl, selected from unsubstituted and substituted imidazolyl, diazolyl, trialzolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl, oxadiazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, triazolopyridyl, purinyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazolyl and triazinyl, wherein the heterocycle may be unsubstituted or substituted by (C1-4) alkyl, (C1-4) alkoxy, halogen, trihalo-(C1-4) alkyl, hydroxy, mercapto, amino, carboxyl, carbamoyl, di-(C1-14) alkylamino, carboxymethyl, carbamoylmethyl, sulfomethyl or methoxycarbonylamino, said process comprising the steps ofi) reacting a compound of formula II in which R is a silyl protecting group, with a compound of the formula P(R4)3 or P(OR4)3 to produce a compound of formula III wherein X is â€”P(R4)3I or â€”P(O)(OR4)2,R is as defined above, and R4 is a (C1-4)alkyl group or an aryl group containing up to 10 carbon atoms; ii) reacting the compound of formula III with a base to produce a compound of formula IV wherein X+ is â€”P+(R4)3 or â€”P(O).(OR4)2Y+,R4 and R are as defined above and Y+ is an alkali metal cation; and iii) reacting a compound of formula IV with a compound of formula V wherein R1 and R2 are as defined above, and splitting off the silyl protecting group R, to produce a compound of formula;the improvement which comprises that the base in step ii) is a weak base selected from: i) a compound formula whereinR5 is hydrogen, (C1-10) alkyl or aryl containing up to 10 carbon atoms and R6 and R7, which may be the same or different, are each an activated group of formula â€”COOR8, â€”CN, â€”SO2R8, â€”COR8 or â€”CON (R8)2; or R5 and R6, which may be the same or different, are each aryl containing up to 10 carbon atoms and R7 is an activated group of formula â€”COOR8, â€”CN, â€”SO2R8, â€”COR8 or â€”CON(R8)2; W+ is an alkali metal cation; and R8 is (C1-10) alkyl, cycloalkyl or aryl containing up to 10 carbon atoms; or ii) a salt of a carboxylic acid of formula R10â€”COOâˆ’W30  in which R10 is (C1-10)alkyl or aryl containing up to 10 carbon atoms; and W+ is defined above, with a compound of formula III in step ii).