反应详情

Sodium hydride (0.256 g, 60% oil dispersion) is added to a solution of tert-butyl 2-(2-(2,3-difluoro-5-iodobenzoyl)-3-ethoxy-3-oxoprop-1-enyl)-1-methylhydrazinecarboxylate (Preparation 33, 3.20 g) in N,N-dimethylformamide (18 mL) at room temperature, and the mixture is stirred for 2 h. The reaction mixture is poured into a mixture of 100 mL of ice water and 100 mL of saturated brine. The mixture is extracted 3 times with ethyl acetate. The combined organic layers are dried (Na2SO4) and concentrated under a nitrogen stream overnight. The crude product is purified by chromatography, using 200 g of silica gel packed and eluted with acetone/CH2Cl2/heptane (1/3/6), provided 2.76 g (90%) of the title compound as a white foam. Physical characteristics: 1H NMR (CDCl3) δ8.50, 8.31, 7.67, 4.32, 3.37, 1.49, 1.34, 1.25; 13C NMR (CDCl3) δ168.87, 163.97, 160.01, 155.50, 141.76, 131.84, 131.37, 128.46, 127.24, 110.98, 86.73, 78.64, 61.47, 36.09, 28.00, 14.64; MS (ESI+) m/z 491 (M+H)+; TLC (silica gel GF): Rf=0.44 acetone/CH2Cl2/hexane (1/1/3).

1. extractionThe mixture is extracted 3 times with ethyl acetate
2. dry with materialThe combined organic layers are dried (Na2SO4)
3. concentrationconcentrated under a nitrogen
4. waitstream overnight
5. customThe crude product is purified by chromatography
6. washeluted with acetone/CH2Cl2/heptane (1/3/6)