Nitromethane → 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

Participants

Reaction Steps

To a stirred solution of tert-butyl 5′-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 6, 6.54 g, 11.658 mmol) in DMF (215 mL) was added nitromethane (6.24 mL, 116.57 mmol) and DBU (1.69 mL, 11.3mmol) at room temperature. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete consumption of starting material, reaction mixture was quenched with water (250 mL) and extracted with ethyl acetate (2×300 mL). Combined organic layer was washed with aqueous LiCl solution (2×400 mL) then brine (500 mL), dried over sodium sulfate and concentrated to get as semi solid (11.23 g, crude). Crude compound was purified by column chromatography using silica gel (230-400 mesh). Desired compound was eluted in 10% ethyl acetate in n-hexane to afford light yellow sticky liquid (4.51 g, 63.7%). 1H NMR (400 MHz, CDCl3) δ: 1.48 (s, 9H), 1.85-1.88 (m, 1H), 2.16-2.17 (m, 1H), 3.40-3.44 (m, 1H), 3.95 (d, J=18.84 Hz, 1H), 4.13-4.18 (m, 2H), 4.33-4.36 (m, 2H), 5.17 (d, J=4.12 Hz, 2H), 7.13 (d, J=6 Hz, 1H), 7.26 (s, 1H), 7.63-7.65 (m, 1H), 7.76-7.78 (m, 1H), 8.00-8.02 (m, 1H). LC-MS (m/z): 605.0 (M−H).

Provenance & Evidence