反应详情

Dimethyl malonate (59.7 g, 0.44 mol) was added dropwise to a stirred solution of potassium tert-butoxide (51 g, 0.44 mol) in dry t-butanol (500 mL). To the resultant suspension, a warm solution of 2-chloro-5-trifluoromethylnitrobenzene (50 g, 0.22 mol) in t-butanol (100 mL) was added and the mixture was refluxed for 6 h (reaction monitored by TLC). After completion of the reaction, most of the t-butanol was distilled off under vacuum, and chilled water was then added to the reaction mixture. The pH was adjusted to neutral with dilute hydrochloric acid, which resulted in the precipitation of the product. The mixture was stirred for 30 minutes and the product was filtered off (68 g, 95%). This material was used without further purification in the next step. A small amount was crystallized (EtOAc/hexane, 4:6) for analysis, to yield a yellow crystalline material, mp 65-67° C. 1H NMR (CDCl3) 8.30 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 5.37 (s, 1H), 3.80 (s, 6H). MS (FAB) m/z: 322.1 (M++1).

1. temperaturethe mixture was refluxed for 6 h
2. custom(reaction monitored by TLC)
3. customAfter completion of the reaction
4. distillationmost of the t-butanol was distilled off under vacuum
5. temperaturechilled water
6. additionwas then added to the reaction mixture
7. customresulted in the precipitation of the product
8. filtrationthe product was filtered off (68 g, 95%)
9. customThis material was used without further purification in the next step
10. customA small amount was crystallized (EtOAc/hexane, 4:6) for analysis
11. customto yield a yellow crystalline material, mp 65-67° C