反应详情

To a solution of (S)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-phenyl]-methanol (340 mg, 1.2 mmol) in methylene chloride (10 mL) at 0° C. was added carbon tetrabromide (485 mg, 1.46 mmol) and stirred for 10 minutes followed by addition of triphenylphosphine (383 mg, 1.46 mmol). Reaction was stirred at 0° C. for 1 hour and allowed to warm to room temperature and stirred for 16 hours. Reaction was concentrated in vacuo and purified on 25+S Biotage column eluting with 0-20% ethyl acetate in heptane (10 CV), 20% (2CV), to yield the title compound (270 mg, 66%) as a colorless oil. This oil solidified upon standing and was recrystalized from hexane to yield crystals (mp=43-45° C.), which were submitted to X-ray crystallography to establish absolute configuration. 1H NMR (400 MHz, CDCl3) δ ppm 1.1 (m, 4H) 1.3 (m, 2H) 1.6 (m, 3H) 1.7 (m, 1H) 2.0 (d, J=12.6, 1H) 3.2 (s, 3H) 4.2 (d, J=7.9, 1H) 4.5 (d, J=10.3 Hz, 1H) 4.6 (d, J=10.3 Hz, 1H) 7.4 (d, J=8.3 Hz, 1H) 7.5 (d, J=8.3 Hz, 1H) 7.6 (s, 1H). [α]D20=−50 deg (c=11.5 mg/mL, acetone)

1. customReaction
2. stirringwas stirred at 0° C. for 1 hour
3. stirringstirred for 16 hours
4. customReaction
5. concentrationwas concentrated in vacuo
6. custompurified on 25+S Biotage column
7. washeluting with 0-20% ethyl acetate in heptane (10 CV), 20% (2CV)