Thionyl Chloride → 2-Fluoro-5-methylbenzoyl chloride

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Reaction Steps

A mixture of 2-fluoro-5-methylbenzoic acid (41.05 g, 0.266 mol) in thionyl chloride (200 mL) is refluxed for 45 min., during which time it becomes homogeneous. After cooling, the thionyl chloride is evaporated to yield 2-fluoro-5-methylbenzoyl chloride, as a yellow liquid, which is dissolved in CH2Cl2 (500 mL), and cooled to 0° C. To this solution is added 2-(trimethylsilyl)-ethanol (48.65 mL, 40.14 g, 0.34 mol), followed by triethylamine (85.86 g, 118.3 mL, 0.85 mol), and the solution is warmed to room temp. over 1 h. The solution is then washed with 1 N HCl (2×500 mL), water (1×250 mL) and brine (1×100 mL), dried (MgSO4), evaporated and chromatographed (silica, 5% EtOAc/hexane) to yield (2-trimethylsilyl)-ethyl 2-fluoro-5-methylbenzoate, as a yellow oil.

Provenance & Evidence