Diisopropylamine → 1-(4-Bromo-3-methylphenyl)-4,4,4-trifluoro-3-(methoxymethylamino)-2-buten-1-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (11.1 mL, 83.3 mmol) in tetrahydrofuran (100 mL) at −78° C. was added 2.5 M n-BuLi in hexanes (33.31 mL, 83.3 mmol). The reaction mixture was allowed to warm to 0° C., stirred for 20 minutes, and then cooled to −78° C. 2-Bromo-3,3,3-trifluoropropene (6.78 g, 38.7 mmol) was added to the reaction mixture, which was stirred for 30 minutes. Then a solution of 4-bromo-N-methoxy-N,3-dimethylbenzamide (i.e. the title product of Step A) (5.0 g, 19.4 mmol) in tetrahydrofuran (20 mL) was added to the reaction mixture at −78° C., which was then warmed to 0° C. Water (25 mL) was added to the mixture, which was then stirred for 1 hour at 0° C. The reaction mixture was extracted with ether and concentrated under reduced pressure, and the oily residue was purified by chromatography on silica gel to afford a mixture of 3-[bis (1-methylethyl)amino]-1-(4-bromo-3-methylphenyl)-4,4,4-trifluoro-2-buten-1-one and 1-(4-bromo-3-methylphenyl)-4,4,4-trifluoro-3-(methoxymethylamino)-2-buten-1-one (2.5:1 ratio by LCMS) (6.55 g, approx. 92% yield) as a bright orange oil.

Provenance & Evidence