n-Butyl lithium → 1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one

Temperature

-78 °C

4-Bromo-1-methyl-1H-pyrazole (41.3 mL, 400 mmol), was dissolved in tetrahydrofuran (750 mL) and cooled to −78° C. N-Butyllithium (2.5 M solution in hexanes, 160 mL, 400 mmol) was added drop-wise over 30 minutes, and the resulting mixture was stirred for 1 hour at −78° C. After drop-wise addition of a solution of N-methoxy-N-methylacetamide (40.9 mL, 400 mmol) in tetrahydrofuran (100 mL) to the −78° C. reaction mixture, the cooling bath was allowed to warm to 0° C. over 4 hours. The reaction was then quenched with saturated aqueous sodium chloride solution (50 mL), and volatiles were removed in vacuo. The residue was diluted with ethyl acetate (1000 mL), treated with magnesium sulfate, and stirred for 30 minutes before being filtered and concentrated in vacuo. Purification was carried out via silica gel chromatography (material was loaded in a minimum amount of dichloromethane; Gradient: 5% to 100% ethyl acetate in heptane) to provide a pale yellow oil that solidified on standing. Yield: 28.5 g, 230 mmol, 57%. 1H NMR (500 MHz, CDCl3) δ 2.37 (s, 3H), 3.90 (s, 3H), 7.83 (s, 1H), 7.84 (s, 1H).

1. customto the −78° C. reaction mixture
2. temperatureto warm to 0° C. over 4 hours
3. customThe reaction was then quenched with saturated aqueous sodium chloride solution (50 mL), and volatiles
4. customwere removed in vacuo
5. additionThe residue was diluted with ethyl acetate (1000 mL)
6. additiontreated with magnesium sulfate
7. stirringstirred for 30 minutes
8. filtrationbefore being filtered
9. concentrationconcentrated in vacuo
10. customPurification
11. customGradient: 5% to 100% ethyl acetate in heptane) to provide a pale yellow oil that

ORD record

ord-fe9c73b799734eafad719ba7d3e27838

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598155B2