反应详情

A solution of NaOEt (freshly prepared from 0.84 g Na and 10 mL of ethanol) was added to diethyl malonate (5.53 mL, 0.036 mol) in 10 mL of ethanol. After stirring for 1 h at room temperature, the resulting solution was added to a suspension of 1-bromo-2-(bromomethyl)-4-chloro-5-(4-ethoxybenzyl)benzene (BJ) (2.8 g, 0.0067 mol) in 10 mL of ethanol and heated to 80° C. overnight. The ethanol was removed by distillation. The remaining solution was cooled to 0° C., diluted with water, and acidified to pH 2 with conc. HCl. The aqueous solution was extracted with ethyl acetate, and the organic layer was washed with water and brine, dried over Na2SO4, concentrated, and the residue was taken up in 40 mL of ethanol and 50 mL of aqueous NaOH solution. The mixture was heated to reflux for 4 h, and then the ethanol was removed by distillation. The solution was cooled to 0° C., acidified with 50 mL of conc. HCl and then heated to reflux overnight. The solution was basified to pH 12 and extracted with ethyl acetate. The aqueous solution was acidified to pH 2 and the precipitate collected. The filter cake was washed with water and dried under vacuum to obtain 1.07 g of intermediate BK.

1. temperatureheated to 80° C. overnight
2. customThe ethanol was removed by distillation
3. temperatureThe remaining solution was cooled to 0° C.
4. additiondiluted with water
5. extractionThe aqueous solution was extracted with ethyl acetate
6. washthe organic layer was washed with water and brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. temperatureThe mixture was heated
10. temperatureto reflux for 4 h
11. customthe ethanol was removed by distillation
12. temperatureThe solution was cooled to 0° C.
13. temperatureheated
14. temperatureto reflux overnight
15. extractionextracted with ethyl acetate
16. customthe precipitate collected
17. washThe filter cake was washed with water
18. customdried under vacuum