Bromide ion → 1,1-Dimethylethyl 4-fluoro-3-[(methylamino)methyl]benzoate

Participants

Reaction Steps

A mixture of tert-butyl 4-fluoro-3-methylbenzoate (9.85 g, 46.9 mmole), N-bromosuccinimide (10 g, 56 mmole), benzoyl peroxide (0.6 g, 2.5 mmole), and CCl4 (100 mL) was heated to reflux with the aid of a 150 W tungsten flood lamp. After refluxing for 24 h, the reaction was cooled to RT and filtered, and the filter pad was washed with CCl4 (25 mL). The filtrate was concentrated to give the crude benzylic bromide (15.11 g, 59% pure by GC, containing 32% dibromide) as a yellow oil. To a solution of this crude bromide in THF (150 mL) was added with stirring at 0° C. a solution of methylamine (40 wt % in H2O, 20 mL, 232 mmole) in one portion. The reaction was allowed to warm to RT and stirred for 18 h, then was concentrated to half its volume. The residue was diluted with H2O (250 mL) and extracted with Et2O (2×150 mL). The combined organic layers were washed sequentially with 1.0 N NaOH (150 mL) and brine (150 mL), dried (Na2SO4), and concentrated. The remaining residue was purified by flash chromatography on silica gel (10% MeOH in 1:1 EtOAc/CHCl3) to give the title compound (4.85 g, 43%) as a yellow oil: MS (ES) m/e 240.0 (M+H)+.

Provenance & Evidence