Carbon Dioxide → 3-Chloro-2-fluoro-5-(trifluoromethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of ethyl magnesium bromide solution (6.25 ml, 6.25 mmol, 1.25 equiv., 1M in THF) and diisopropyl amine (77.7 μl, 0.5 mmol, 0.1 equiv.) was added 3-chloro-4-fluoro-benzo trifluoride (0.99 g, 5 mmol in THF (2 ml)) at ambient temperature and the mixture was heated in an oil bath to 50° C. for 13 h. The brown clear reaction mixture was cooled to 0-5° C., was transferred into a syringe and added dropwise to a solution of CO2 (2.2 g, 50 mmol, 10 equiv.) in THF (5 ml) at −70° C. and stirred for 15 min. To the brown suspension was added HCl (1M, 14 ml) and the phases were separated. The aqueous phase was extracted with TBME (10 ml), the combined organic phases were dried over sodium sulfate, filtered, washed with TBME and the solvents were removed under vacuum to yield a dark brown oil (0.97 g of the crude product). The crude product was treated with methyl cyclohexane (4.4 ml) and heated in a pre-heated oil bath to reflux. After 5 min, a brown clear solution was obtained, the oil bath was removed, the reaction mixture was cooled to ambient temperature and the formed suspension was stirred overnight at ambient temperature. After 18 h the brown suspension was stirred in an ice bath (0-5° C.) for two hours, the obtained crystals were filtered off, the crystals were washed with cold methyl cyclohexane (1.6 ml) and the crystals were dried until weight constancy to yield the product as white crystals (0.46 g, 38.2% yield).

Provenance & Evidence