tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate → tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)-3,4-di hydro-2H-pyrrol-5-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Participants

Reaction Steps

To the solution of tert-butyl 5′-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 7, 1.2 g, 1.98mmol) in ethanol (10 mL) nitrogen was purged for 30 minutes and was added pre-washed Raney-Nickel (0.24 g, 50% suspension in water). Resulting reaction mixture was stirred under hydrogen atmosphere using balloon for 16 hours at room temperature. After complete conversion of starting material, the reaction mixture was filtered through celite bed. The bed was washed with 10% MeOH in DCM (30 mL). Combined filtrate was concentrated under vacuum to get 1.1 g of crude, off white solid. Crude compound was purified by column chromatography on silica gel (230-400 mesh). Desired compound was eluted in 7% EtOAc in n-Hexane to afford off white semi solid (451 mg, 40.63%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.44 (d, J=17.2 Hz 1H), 3.76-3.81 (m, 1H), 4.13 (d, J=9.68 Hz, 2H), 4.32 (d, J=9.68 Hz, 2H), 4.42 (d, J=17.12 Hz 1H), 4.84-4.89 (m, 1H), 5.13 (s, 2H), 7.32 (d, J=5.96 Hz, 2H), 7.54 (d, J=7.92 Hz 1H), 7.73 (s, 1H), 7.83 (d, J=7.88 Hz 1H). LC-MS (m/z): 558.8 (M+H).

Provenance & Evidence