反应详情

温度

75 °C

A pressure tube was dried with a heat gun under nitrogen. The pressure tube was charged in the following order with isobutyraldehyde 2(0.262 g, 3.63 mmol), dimethylformamide (3 mL), t-butylacetoacetate 1 (0.574 g, 3.63 mmol), 3-aminopyrazole 3 (0.362 g, 4.36 mmol) and sodium acetate (1.22 g, 14.5 mmol). The mixture was flushed with nitrogen. The tube was sealed and warmed to 75° C. and stirred overnight. The mixture was cooled to room temperature, diluted with ethyl acetate to a volume of 20 mL, washed with lithium chloride (2.4M, 10 mL) and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 1.02 of a yellow oil. The oil was purified by flash chromatography (silica, 45% ethyl acetate/heptane) to give 0.42 g (41% yield) of the title compound. Reverse Phase HPLC: YMC S5 ODS 4.6×50 mm Ballistic column, UV detection at 220λ, 4 min. gradient 0-100% Solvent B/A (Solvent A: 10% MeOH/H2O with 0.2% PPA, Solvent B: 90% MeOH/H2O with 0.2% PPA), 4 mL/min. Rt=3.83 min, (100% pure). Reverse Phase LC/MS: YMC S5 ODS 4.6×50 mm Ballistic column, UV detection at 220λ, 4 min. gradient 0-100% Solvent B/A (Solvent A: 10% MeOH/H2O with 0.1% TFA, Solvent B: 90% MeOH/H2O with 0.1% TFA), 4 mL/min. Rt=3.06 min. MS (EM, M+1: 278). HMR (CDCl3, 400 MHz): 7.37(1H,d,J=2.2 Hz), 6.35(1H,s), 5.55(1H,d,J=1.8 Hz), 5.29(1H,d,J=2.2 Hz), 2.41(3H,s), 1.50(9H,s), 1.28-1.19(1H,m), 1.07(3H,d,J=7.0 Hz), 0.60(3H,d,J=7.0 Hz).

1. customA pressure tube was dried with a heat gun under nitrogen
2. customThe mixture was flushed with nitrogen
3. customThe tube was sealed
4. temperatureThe mixture was cooled to room temperature
5. additiondiluted with ethyl acetate to a volume of 20 mL
6. washwashed with lithium chloride (2.4M, 10 mL) and brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto give 1.02 of a yellow oil
11. customThe oil was purified by flash chromatography (silica, 45% ethyl acetate/heptane)