反应详情

温度

100 °C

2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide (1.67 g, 10 mmol) was dissolved in DMF (17 ml). (S)-4-Chloromethyl-2,2-dimethyl-[1,3]dioxolane (1.52 g, 10 mmol) was added into the mixture. Finally Sodium tert-butoxide (0.98 g, 10 mmol) was added at room temperature. The mixture was heated to 100° C. with agitation for 23 hours under N2 atmosphere. UPLC indicated that there was 26% 2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide remained in the mixture. Additional 2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide (0.76 g, 5 mmol) and Sodium tert-butoxide (0.49 g, 5 mmol) was added. The mixture was stirred at 100° C. for another 24 hrs. HPLC indicated 2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide was 9.4% remained, the selectivity of N1/N2 alkylation products was 2.8:1. The DMF was concentrated under reduced pressure. Water (10 ml) was added. The mixture was extracted with DCM (2×12 ml), the organic layer was washed with 10% aqueous NaCl (2×20 ml). The organic layer was dried over Na2SO4, concentrated under reduced pressure to give oil, which is purified by silicon column (hexane/EA=5:1 to hexane/EA=3:1) to give off-white solid (0.84 g), yield: 30%. 1H-NMR (400 MHz, d6-DMSO): δ 9.85 (s, 1H), 7.59 (s, 1H), 6.47 (s, 1H), 4.36-4.39 (m, 1H), 4.08-4.12 (m, 2H), 4.0-4.02 (m, 1H), 3.73-3.75 (m, 1H), 1.33 (s, 3H), 1.26 (s, 3H), 1.19 (s, 9H).

1. concentrationThe DMF was concentrated under reduced pressure
2. additionWater (10 ml) was added
3. extractionThe mixture was extracted with DCM (2×12 ml)
4. washthe organic layer was washed with 10% aqueous NaCl (2×20 ml)
5. dry with materialThe organic layer was dried over Na2SO4
6. concentrationconcentrated under reduced pressure
7. customto give oil, which
8. customis purified by silicon column (hexane/EA=5:1 to hexane/EA=3:1)