Ethyl 3,3,3-trifluoro-2-oxopropanoate → HCID 90780200, compound

Participants

Reaction Conditions

Reaction Steps

5.7 g (29.3 mmol) of 3-fluoro-2-methyl-6-(1-methylenepropyl)anisole, 7.7 ml (170 mmol) of ethyl trifluoropyruvate and 15 g of molecular sieve are admixed dropwise at 0° C. over 30 minutes with 0.76 g (0.88 mmol) of [Cu(R,R)-2,2-bis(4,5-dihydro-4-tert-butyloxazolin-2-yl)propane)(H2O)2]((SbF6)2, in 38 ml of dichloromethane. The reaction mixture is stirred at 0° C. for 16 hours and the reaction mixture is purified by means of column chromatography on silica gel (hexane/ethyl acetate 0-20%). This gives 8.7 g of ethyl (R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hex-4-enoate as an E/Z mixture with an enantiomeric excess of greater than 80%, and in this way 13.9 of crude E/Z-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-(trifluoromethyl)hex-4-ene-1,2-diol. 4.0 g (11 mmol) of ethyl (2R,4E/Z)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hex-4-enoate are dissolved in 180 ml of 2,2,2-trifluoroethanol and the solution is admixed with 400 mg of palladium on carbon (10%). The suspension is shaken under a hydrogen atmosphere at 100 bar until reaction is complete. The mixture is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. The concentrated crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 15%) to give 3.7 g (10 mmol) of ethyl (2R,4R/S)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanoate as a diastereomer mixture. 3.7 g (10 mmol) of ethyl (2R,4R/S)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanoate are cooled to −15° C. in 132 ml of diethyl ether and admixed over 10 minutes with solid lithium aluminum hydride, 1.03 g (27.3 mmol), in portions. The mixture is stirred at −10° C. for 3 hours, and ethyl acetate and water are added cautiously. The suspension is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate.

Provenance & Evidence