Benzoyl Peroxide → methyl 3-(bromomethyl)-5-fluorobenzoate

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br:13]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:13][CH2:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([F:1])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

Procedure

To a solution of methyl 3-fluoro-5-methylbenzoate (1.64 g, 9.75 mmol, from Step 1) and N-bromosuccinimide (2.05 g, 11.5 mmol) in carbon tetrachloride (20 mL) was added benzoyl peroxide (0.1 g, 0.6 mmol) and the mixture was heated to reflux for four hours. The reaction was then cooled to room temperature, filtered, and diluted with DCM. The solution was washed successively with sodium thiosulfate, 1N NaOH, water, and brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography, eluting with a gradient from 0-20% ethyl acetate in hexanes, afforded a partially purified product. The cleanest fractions were used in the displacement with amine in Step 3. 1H NMR (300 MHz, CDCl3): δ 7.87-7.85 (m, 1H), 7.68-7.62 (m, 1H), 7.31 (ddd, 1H), 4.47 (s, 2H), 3.93 (s, 3H).