反应详情

To a suspension of NaH (0.37 g, 15.4 mmol, 60.0% dispersion in oil) in DMF (40 mL) was added a solution of di-t-butyl malonate (3.6 g, 16 mmol) in DMF (10 mL) at 0° C. and this was stirred for 15 minutes. Subsequently, 2-bromo-4-fluorobenzonitrile (3.0 g, 15.0 mmol) was added in one portion and the reaction mixture was stirred for 8 hours at 80° C. and three hours at room temperature. Water (50 mL) was added and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over MgSO4 and filtered. After evaporation in vacuo, the residue was purified by flash chromatography (20% EtOAc in hexane) to give di-tert-Butyl(3-bromo-4-cyanophenyl)malonate as a light brown solid. 1H NMR (500 MHz, DMSO-d6) δ 7.97 (d, J=8 Hz, 1H), 7.88 (s, 1H), 7.60 (d, J=8 Hz, 1H), 4.95 (s, 1H), 1.42 (s, 18H). LC-MS (IE, m/z): 398 [M+1]+.

1. stirringthe reaction mixture was stirred for 8 hours at 80° C. and three hours at room temperature
2. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
3. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customAfter evaporation in vacuo
7. customthe residue was purified by flash chromatography (20% EtOAc in hexane)