Tetrahydrofuran → 2-(2,6-Difluoro-4-methoxyphenyl)-1,1,1-trifluoropropan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a THF (100 ml) solution of 1,3-difluoro-5-methoxybenzene (7 g, 48.6 mmol) was added dropwise 1.6 M hexane solution of n-butyllithium (30 ml, 48.6 mmol) at −78° C. over 30 minutes and the mixture was stirred for 2 hours at −78° C. Then 1,1,1-Trifluoroacetone (6.5 g, 58.3 mmol) was added at −78° C. and the mixture was stirred for 2 hours at −78° C. After stirring at room temperature for an additional 1 hour, the reaction was quenched with water. The whole was extracted with EtOAc and the organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel column chromatography eluting with hexane/EtOAc (10:1) gave the title compound (9.7 g, 78% yield) as a colorless oil.

Provenance & Evidence