Water → 3-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidine

Participants

Reaction Steps

To a stirred solution of 1-benzyl-3-(3,5-dichloro-phenyl)-3-trifluoromethyl-pyrrolidine (Preparation 34, 7.5 g, 20.1 mmol) in 1.2-dichloroethane (50 mL) was added 1-chloroethyl chloroformate (3.87 mL, 36.19 mmol) at room temperature. Resulting reaction mixture was refluxed for 3 hours. After complete consumption of starting material, reaction mixture was concentrated under reduced pressure to afford brown thick oil, which was dissolved in MeOH (50 mL) and refluxed for 2 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to afford brown oil, to which water was added (100 mL) and extracted with hexane (2×50 mL). Aqueous layer was basified by saturated sodium bicarbonate solution and extracted by ethyl acetate (3×50 mL). Combined organic layer was dried over anhydrous sodium sulfate, concentrated in vacuo to afford brown oil (7.5 g, crude). Crude compound was purified by column chromatography (100-200 mesh silica). Desired product was eluted in 25% ethyl acetate in hexane to afford product as brown oil (5.1 g, 89.32%). 1H-NMR (400 MHz, DMSO-d6) δ: 2.33-2.39 (m, 1H), 2.40-2.45 (m, 1H), 2.85-2.98 (m, 2H), 3.34 (d, 1H, J=12.72 Hz), 3.52 (d, 1H, J=12.56 Hz), 7.28-7.34 (m, 1H), 7.46-7.52 (m, 2H), 7.64 (d, 1H J=1.25 Hz). (m/z): 284.0 (M+H).

Provenance & Evidence