反应详情

温度

75 °C

NaH (345 mg, 60% in mineral oil, 8.6 mmole, 1.05 equiv.) is added to a stirred solution of 2-(4-bromo-2,5-difluoro-benzyl)-3-cyclopropylamino-3-methylsulfanyl-acrylic acid ethyl ester (4, 3.46 g, 8.2 mmole) in DMF (anhydrous, 100 ml). The reaction mixture is stirred at 75° C. for 18 hours (TLC is used to indicate reaction completion). The reaction mixture is cooled, diluted with NH4Cl solution, and extracted with EtOAc. The organics are washed with brine (4×30 ml), dried over Na2SO4, and concentrated in vacuo to give 5 as a light yellow solid. This intermediate is used without further purification 1H NMR (CDCl3) indicated >98% purity). 1HNMR (CDCl3) δ: 8.09 (d, 1H), 7.90 (d, 1H), 4.35 (q, 2H), 3.22 (m, 1H), 2.49 (s, 3H), 1.3-1.5 (m, 7H).

1. custom(TLC is used to indicate reaction completion)
2. temperatureThe reaction mixture is cooled
3. extractionextracted with EtOAc
4. washThe organics are washed with brine (4×30 ml)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo