反应详情

温度

0 °C

Diethyl malonate (8.33 mL, 54.59 mmol) was added dropwise to sodium hydride (60% oil dispersion) (2.28 g, 56.97 mmol) in DMF (55 mL) at 0° C. The mixture was stirred for 5 min at ambient temp, wherafter 1-bromo-2-(bromomethyl)-3-chlorobenzene (13.5 g, 47.5 mmol) dissolved in DMF (15 mL) was added dropwise at 0° C. The mixture was stirred at 0° C. for 20 min and ambient temp overnight. NH4Cl (aq) was added to quench the reaction. Diethyl ether was added followed by water. The phases were separated and the aqueous phase was extracted with diethyl ether. The combined organic phases were washed with brine and dried (MgSO4). The aqueous phase was extracted with dichloromethane. The organic phase was washed with brine. The solvents were evaporated to give 18.2 g (quantitative). 4 g of the crude material was dissolved in dichloromethane and purified by column chromatography eluting with gradients of ethyl acetate in heptanes. Fractions containing product were pooled and the solvents were evaporated to give the title compound. Yield: 3.32 g, 19%. 1H NMR (400 MHz, CDCl3) δ ppm 1.23 (t, 7H) 3.62 (d, 2H) 3.84 (m, 1H) 4.20 (q, 4H) 7.06 (t, 1H) 7.35 (dd, 1H) 7.50 (dd, 1H). MS (ES+) m/z 365 [M+H]+.

1. additionwas added dropwise at 0° C
2. customto quench
3. customthe reaction
4. customThe phases were separated
5. extractionthe aqueous phase was extracted with diethyl ether
6. washThe combined organic phases were washed with brine
7. dry with materialdried (MgSO4)
8. extractionThe aqueous phase was extracted with dichloromethane
9. washThe organic phase was washed with brine
10. customThe solvents were evaporated
11. customto give 18.2 g (quantitative)
12. custompurified by column chromatography
13. washeluting with gradients of ethyl acetate in heptanes
14. additionFractions containing product
15. customthe solvents were evaporated