(Trifluoromethyl)benzene → tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

In 100 mL two neck RBF equipped with dean-stark apparatus a stirred solution of tert-butyl 5′-acetyl-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 1, 4.5 g, 14.851 mmol) in toluene (13.5 mL) and trifluorotoluene (13.5 mL) was added 2,2,2-trifluoro-1-(3,4,5-trichlorophenyl)-ethanone (4.44 g, 17.079 mmol) and Cs2CO3 (0.483 g, 1.485 mmol) at room temperature. Resulting reaction mixture was heated at 110° C. for 16 hours. After complete consumption of starting material, reaction mixture was diluted with ter-butylmethyl ether (30 mL) and filtered through celite bed. Filtrate was concentrated under vacuum to afford brown sticky oil (9.01 g, crude). Crude compound was purified by column chromatography using silica gel (230-400 mesh). Desired compound was eluted in 20% ethyl acetate in n-hexane to give light yellow solid (6.54 g, 80.64%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 4.10 (d, J=9.52 Hz, 2H), 4.32 (d, J=9.36 Hz, 2H), 5.12 (s, 2H), 7.20 (d, J=9.76 Hz, 2H), 7.39 (s, 1H), 7.56 (d, J=7.96 Hz, 1H), 7.67 (s, 1H), 7.84 (d, J=7.96 Hz, 1H). LC-MS (m/z): 374.1 (M+H).

Provenance & Evidence