tert-Butanol → Cyclobutanecarboxylic acid, 3,3-difluoro-, 1,1-dimethylethyl ester

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Reaction Steps

3,3-difluorocyclobutanecarboxylic acid (1.0 g, 7.3 mmol) was dissolved in DCM (10 mL) and cooled in an ice bath. To the solution was added N,N-dimethylpyridin-4-amine (92 mg, 0.735 mmol) portionwise followed by 2-methylpropan-2-ol (1.1 g, 14.7 mmol) in one portion. A 1M solution of N,N′-dicyclohexylcarbodiimide in DCM (8.1 mL, 8.1 mmol) was added dropwise keeping the temperature below 10° C. The resulting slurry was warmed up to room temperature and stirred for 18 hours. The solid was removed by filtration and the filtrate was washed with 2N aqueous HCl solution (2×15 mL), water (2×15 mL), and then saturated aqueous NaHCO3 solution (2×15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to give 1.49 g of a crude product as a mixture of white solid and yellow oil. To the mixture was added pentane (30 mL) and the mixture as then filtered through a silica gel pad eluting with pentane to give the title compound (896 mg, 63%) as colourless oil.

Provenance & Evidence