Hydrochloric Acid → 3-(4-Bromophenyl)4-(3-fluoro-4-methylthiophenyl)-5-methyl-4,5-dihydro-5-isoxazolol

To a solution of 1-(4-bromophenyl)-2-(3-fluoro-4-methylthiophenyl)ethanone oxime (1.56 g, 4.42 mmol) in tetrahydrofuran (10 ml) was added dropwise 9.7 ml (9.70 mmol) of 1 M lithium N,N-diisopropylamide in tetrahydrofuran and hexane, which was prepared from N,N-diisopropylamine and 1.6 M n-butyl lithium in hexane, over 0.5 h at −78˜−50° C. After 1 h, a solution of N-acetyl imidazole (584 mg, 5.31 mmol) in tetrahydrofuran (10 ml) was added to the mixture at the same temperature. The resulting mixture was allowed to warn up to room temperature and stirred for further 1 h. Then, the mixture was acidified with 2M hydrochloric acid (˜30 ml) and extracted with diethyl ether (150 ml). The separated organic layer was washed with saturated sodium bicarbonate (50 ml×2) and water (50 ml), dried over magnesium sulfate, and evaporated. The obtained oily residue was chromatographed on a column of silica gel (80 g) as eluting with ethyl acetate/hexane (1/4) to afford 632 mg (36%) of the title compound as a colorless oil.

1. customto warn up to room temperature
2. extractionextracted with diethyl ether (150 ml)
3. washThe separated organic layer was washed with saturated sodium bicarbonate (50 ml×2) and water (50 ml)
4. dry with materialdried over magnesium sulfate
5. customevaporated
6. customThe obtained oily residue was chromatographed on a column of silica gel (80 g)
7. washas eluting with ethyl acetate/hexane (1/4)

ORD record

ord-4dfa3c3c8452484aa80fce7fc046a5f8

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06294558B1