反应详情

温度

0 °C

A solution containing N,N-dimethylformamide (0.22 mL, 2.85 mmol) and tetrahydrofuran (10 mL) was chilled to 0° C. under nitrogen. While stirring, oxalyl chloride (156 μL, 1.80 mmol) was added, gas evolution was observed followed by a white precipitate. The mixture was stirred at 0° C. for 5 min and at 25° C. for 15 min. The mixture was chilled to −5° C. and the 3-hydroxy-3-methyl-butyric acid (224 mg, 1.90 mmol) was added as a solution in tetrahydrofuran (3 mL) and the mixture was allowed to stir for 10 min. 3-Nitro-1H-pyrazole (prepared in example 3, 200 mg, 1.77 mmol) was dissolved in anhydrous N,N-dimethylformamide (4 mL) and a 60% dispersion of sodium hydride in mineral oil (78 mg, 1.95 mmol) was added while stirring under nitrogen. After the effervescence ceased and the mixture was stirred for an additional 10 min, the mixture was added to the 3-hydroxy-3-methyl-butyric acid solution at −5° C. and continued to stir at 0° C. for 2 h. The mixture was diluted with ethyl acetate (100 mL), washed with water (2×25 mL), saturated aqueous brine solution (25 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 40 g; 15% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded 3-hydroxy-3-methyl-1-(3-nitro-pyrazol-1-yl)-butan-1-one (101 mg, 27%) as a clear oil: H1-NMR (400 MHz, CDCl3) δ 1.42 (6H, s), 3.41 (2H, s), 7.05 (1H, d, J=2.8 Hz), 8.34 (1H, d, J=2.8 Hz).

1. stirringThe mixture was stirred at 0° C. for 5 min and at 25° C. for 15 min
2. temperatureThe mixture was chilled to −5° C.
3. stirringto stir for 10 min
4. stirringwhile stirring under nitrogen
5. stirringthe mixture was stirred for an additional 10 min
6. stirringto stir at 0° C. for 2 h
7. washwashed with water (2×25 mL), saturated aqueous brine solution (25 mL)
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 40 g; 15% ethyl acetate/hexanes to 100% ethyl acetate/hexanes)