反应详情

温度

-70 °C

1 g (6.2 mmol) 3-Chloro-2-fluoroanisole in 10 ml THF are cooled to −70° C. and 2.7 ml of a 2.5 M n-butyl lithium solution in hexane are added. After 1.5 hours at −70° 1 g (6.9 mmol) N,N′-dimethoxy-N,N′-dimethyl urea in 6 ml THF are added at −70° C. and the mixture is stirred another hour at −70° C. 7.5 ml of a 2 M aqueous HCl are added and the reaction is warmed to ambient temperature over 18 hours. The reaction mixture is partitioned between diethyl ether and water. The aqueous phase is extracted with diethyl ether, the combined organic phases are washed with brine, dried over sodium sulfate and evaporated. The crude product is purified by chromatography on silica gel (ethyl acetate in hexane 0 to 30%) to yield 0.59 g 4-chloro-3-fluoro-2,N-dimethoxy-N-methylbenzamid. 1H-NMR (CDCl3); δ=3.35 (br, 3H), 3.49 (br, 3H), 3.98 (s, 3H), 6.99 (dd, 1H), 7.13 (dd, 1H).

1. temperaturethe reaction is warmed to ambient temperature over 18 hours
2. customThe reaction mixture is partitioned between diethyl ether and water
3. extractionThe aqueous phase is extracted with diethyl ether
4. washthe combined organic phases are washed with brine
5. dry with materialdried over sodium sulfate
6. customevaporated
7. customThe crude product is purified by chromatography on silica gel (ethyl acetate in hexane 0 to 30%)