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

ORD record

ord-80461f22d4eb4a11ac346cfddc498109

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949536B2