Acetic Acid → 3-Fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)nitrobenzene

Participants

Reaction Steps

A solution of 1-(diphenylmethyl)-3-methoxy-3-methylazetidine (2.20 g, 8.2 mmol) in 25% tetrahydrofuran/ethanol was treated with glacial acetic acid (1.60 g, 1.50 mL, 24.7 mmol) and then palladium hydroxide on carbon (0.220 g) under a nitrogen stream. The reaction mixture was shaken on a Parr apparatus under 35 psi of H2. At this time TLC analysis (9:1 hexane/ethyl acetate) revealed the reaction to be complete. The mixture was filtered through Celite® (ethyl acetate wash) and the filtrate concentrated in vacuo to give an oil. This material was dissolved in dimethyl sulfoxide (15 mL) and the solution treated with dipotassium hydrogen phosphate (8.60 g, 49.2 mmol) and 3,4-difluoronitrobenzene (1.30 g, 0.886 mL, 8.0 mmol) at ambient temperature. The yellow reaction mixture was stirred at ambient temperature under a nitrogen atmosphere for 18 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and dried in vacuo to give a yellow solid. Chromatography over silica gel, eluting with 8:1 hexane/ethyl acetate, afforded, after concentration of appropriate fractions, 1.80 g (90%) of the title compound as a yellow solid with mp 110°-111° C. and MS(EI) 240 (M+).

Provenance & Evidence