反应详情

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).

1. temperaturethe mixture was heated
2. temperatureto reflux for four hours
3. filtrationfiltered
4. additiondiluted with DCM
5. washThe solution was washed successively with sodium thiosulfate, 1N NaOH, water, and brine
6. dry with materialdried over sodium sulfate
7. customdecanted
8. concentrationconcentrated
9. washFlash chromatography, eluting with a gradient from 0-20% ethyl acetate in hexanes
10. customafforded a partially purified product