反应详情

温度

80 °C

To a stirred suspension of 4-fluoro-2-(methylsulfonyl)benzonitrile (prepared according to the procedure described in Anthonyl, N. J. et al PCT Appl. WO 02/30931, 2002) (2.2 g, 11 mmol) and N-methylhydroxylamine hydrochloride (1.66 g, 20 mmol) in 1:1 water/ethanol (40 mL) was added sodium carbonate (1.06 g, 10 mmol) in small portions and the resulting mixture stirred at 80° C. for 3 h. The reaction mixture was concentrated and the residue was re-dissolved into 1:1 water :ethanol (50 mL). To this solution was added diethyl acetylene-dicarboxylate (1.92 mL, 12 mmol) and the resulting mixture stirred for 30 min at room temperature. The reaction mixture was then taken-up into ethyl acetate (150 mL), washed successively with water and brine (50 mL each), dried (MgSO4), filtered and concentrated to give yellow oil. The crude product was purified on silica gel column (3:7 to 2:3 ethyl acetate/hexanes) to afford the title product as a white solid (2.9122 g, 64% yield). 1HNMR (500 MHz, CDCl3) δ: 7.89 (1H, dd, J=8.09, 2.59 Hz), 7.62 (1H, dd, J=8.39, 5.04 Hz), 7.40 (1H, td, J=8.24, 2.44 Hz), 4.35–4.26 (2H, m), 4.19–4.13 (2H, m), 3.40 (3H, s), 3.38 (1H, d, J=16.17 Hz), 3.15 (1H, d, J=16.17 Hz), 3.02 (3H, s), 1.36–1.30 (3H, m), 1.27–1.23 (3H, m). HRMS (ESI) calcd for C17H22FN2O7S (M+H): 417.1132; found: 417.1116.

1. customprepared
2. concentrationThe reaction mixture was concentrated
3. dissolutionthe residue was re-dissolved into 1:1 water
4. stirringthe resulting mixture stirred for 30 min at room temperature
5. washtaken-up into ethyl acetate (150 mL), washed successively with water and brine (50 mL each)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give yellow oil
10. customThe crude product was purified on silica gel column (3:7 to 2:3 ethyl acetate/hexanes)