Process for preparing 5,5-dimethyl-4-[(4-methylsulphonyl)phenyl]-2-(5H)-furanone derivatives which are useful as cox-2 inhibitors

摘要

The process for preparing a 5,5-dimethyl-4-[(4-methylsulphonyl)phenyl]-2-(5H)-furanone derivative of formula I comprises: a) reacting a thioanisole Me-S-phenyl in a non-reactive solvent and in the presence of a Lewis acid with isobutyryl chloride (Me)2CH-COCl to yield a compound of formula II; b) reacting the compound II with a brominating agent in a non-reactive solvent in the presence of a second solvent such as ethyl acetate to yield a compound of formula III; c) oxidising the compound III in a non-reactive solvent with an oxidising agent optionally in the presence of a suitable catalyst to yield a compound of formula IV; d) reacting the compound IV in an alkanol solvent with a compound of formula V HO-C(O)-CH2-O-R1 in the presence of a suitable base to yield a compound of formula VI; e) reacting the compound VI in an aprotic solvent with a strong base to yield a cyclized compound of formula VII which after dehydration in the presence of a water scavenger yields a compound of formula I. In the above formulae: R1 is alkyl or optionally substituted phenyl or naphthyl. The water scavenger can be isopropyl trifluoroacetate; the aprotic solvent can be acetonitrile and the strong base can be 1,8-diazabicyclo[5.4.0]undec-7-ene.