Patent ID: 6043375
Filing Date: 2000-03-28
Classification: C07D

Abstract:
A process of preparing a taxoid of formula III: ##STR16## in which R represents a hydrogen atom or an acetyl radical,R.sub.1 represents a benzoyl radical or a R.sub.2 --O--CO-- radical in which R.sub.2 represents:a straight or branched alkyl radical having 1 to 8 carbon atoms, an alkenyl radical having 3 to 6 carbon atoms, a cycloalkyl radical having 3 to 6 carbon atoms, or a cycloalkenyl radical having 4 to 6 carbon atoms, these radicals being unsubstituted or substituted with one or more substituents selected from halogen atoms, hydroxyl radicals, alkyloxy radicals having 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion has 1 to 4 carbon atoms, piperidino, morpholino and 1-piperazinyl (unsubstituted or substituted at position 4 with an alkyl radical having 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion has 1 to 4 carbon atoms) radicals, cycloalkyl radicals having 4 to 6 carbon atoms, alkenyl radicals having 4 to 6 carbon atoms, cyano, and carboxyl or alkyloxycarbonyl radicals in which the alkyl portion has 1 to 4 carbon atoms,or a phenyl radical unsubstituted or substituted with one or more atoms or radicals selected from halogen atoms, alkyl radicals having 1 to 4 carbon atoms, or alkyloxy radicals having 1 to 4 carbon atoms;or a saturated or unsaturated nitrogen-containing 5- or 6-membered heterocyclic radical, unsubstituted or substituted with one or more alkyl radicals having 1 to 4 carbon atoms; andR'.sub.5 represents an alkenyl radical having 2 to 8 carbon atoms unsubstituted or substituted with a phenyl radical, an alkynyl radical having 2 carbon atoms, or a phenyl, formyl, alkanoyl, aroyl, hydroxymethyl, carboxyl, or alkoxycarbonyl radical, wherein the aryl portion of the aroyl radical is phenyl and the alkyl portion of the alkanoyl and alkoxycarbonyl radicals contains 1 to 4 carbon atoms;wherein the taxoid of formula III is formed by esterifying protected baccatin III or deacetylbaccatin III using an oxazolidinecarboxylic acid of formula I, or an acid halide or acid anhydride thereof: ##STR17## in which: R' represents a hydrogen atom, an alkali metal or alkaline-earth metal atom, or an alkyl radical having 1 to 4 carbon atoms,R.sub.1 is defined above;R.sub.3 and R.sub.4, which may be identical or different, represent:a hydrogen atom, an alkyl radical having 1 to 4 carbon atoms, an aralkyl radical in which the alkyl portion has 1 to 4 carbon atoms and the aryl portion is substituted with one or more alkoxy radicals having 1 to 4 carbon atoms, or an aryl radical substituted with one or more alkoxy radicals having 1 to 4 carbon atoms; orR.sub.3 represents an alkoxy radical having 1 to 4 carbon atoms, a trihalomethyl radical, or a phenyl radical substituted with a trihalomethyl radical and R.sub.4 represents a hydrogen atom; orR.sub.3 and R.sub.4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring;wherein after the esterification, the protecting groups are replaced by hydrogen atoms,and wherein the esterification is carried out under one of the following conditions:a) prior to the esterification, the iodine atom of the compound of formula I is replaced with a substituent defined by R'.sub.5, orb) the esterification is carried out using a compound according to formula I, and after the protecting groups are replaced by hydrogen atoms, the iodine atom is replaced with a substituent defined by R'.sub.5.