6-(TRIFLUOROMETHYL)PYRID-2-ONE - DEVELOPMENT AND SCALE-UP OF A RING SYNTHESIS ROUTE BASED ON TRIFLUOROACETIC-ANHYDRIDE

Three routes to 6-(trifluoromethyl)pyrid-2-one involving de novo synth esis of the pyridine ring have been investigated which would potential ly allow rapid semi-technical scale manufacture, A route starting from ethyl 4,4,4-trifluoroacetoacetate (beta-keto ester route) has been de monstrated, Development of the route was attempted; however, poor yiel ds at a number of stages and scale-up difficulties made this route una ttractive for commercial use, A four-stage route starting from trifluo roacetic anhydride and an alkyl vinyl ether (TFAA route) has been deve loped which gives good yields and productivity for all stages, The fin al stage of this route is a difficult decarboxylation of a nicotinic a cid derivative, but an 80% yield of the required pyridone with a purit y of > 99.5% could be achieved without a separate purification stage, The route was scaled up to 2000 L, and several hundred kilograms of pr oduct was prepared.