反应详情

To a solution of 1-(2,3-difluorobenzyl)pyrrolidin-2-one (17.05 mL, 89 mmol) in 1,2-dichloroethane (DCE) (240 mL) under nitrogen atmosphere was added dropwise in 15 min POCl3 (12.39 mL, 133 mmol) and the mixture was stirred at ambient temperature for 1 h. Then diethyl 2-(1-aminoethylidene)malonate (19.62 g, 97 mmol) was added and the mixture was heated to 40° C. under nitrogen atmosphere for 22 h. Saturated NaHCO3/water was carefully added (400 mL) and the mixture was stirred at ambient temperature for 1 h then extracted with dichloromethane. The aqueous phase was extracted with dichloromethane and the combined organic phase was washed brine, dried (Na2SO4), concentrated, dried in vacuo to provide (E)-diethyl 2-(1-((1-(2,3-difluorobenzyl)pyrrolidin-2-ylidene)amino)ethylidene)malonate (36.48 g, 70.3 mmol, 79% yield) as a yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.07-1.36 (m, 6 H), 1.88-2.10 (m, 2 H), 2.18-2.27 (m, 3 H), 2.35-2.61 (m, 2 H), 3.13-3.43 (m, 2 H), 3.98-4.30 (m, 4 H), 4.45-4.64 (m, 2 H), 6.94-7.20 (m, 3 H); LCMS (m/z) ES+=395 (M+1).

1. temperaturethe mixture was heated to 40° C. under nitrogen atmosphere for 22 h
2. stirringthe mixture was stirred at ambient temperature for 1 h
3. extractionthen extracted with dichloromethane
4. extractionThe aqueous phase was extracted with dichloromethane
5. washthe combined organic phase was washed brine
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated
8. customdried in vacuo