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温度

0 °C

Diisopropylethylamine (0.14 mL, 0.75 mmol) was added to a suspension of 4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride (0.10 g, 0.25 mmol) in CH2Cl2 (7 mL). The mixture was cooled to 0° C. in an ice bath, and isopropyl chloroformate (1.0M in toluene, 0.28 mL, 0.28 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature, and stirred overnight. The mixture was then concentrated to give the crude product as a colorless oil. The crude product was purified by chromatography on a silica gel column eluted with 5:6 EtOAc/hexane to give 0.11 g (98%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.80-7.70 (m, 2H), 7.65-7.55 (m, 1H), 7.50 (d, 2H, J=8.8 Hz), 6.98 (d, 2H, J=8.6 Hz), 4.92 (septet, 1H, J=6.1 Hz), 4.25-4.15 (m, 2H), 3.86 (d, 2H, J=6.3 Hz), 3.09 (s, 3H), 2.85-2.75 (m, 2H), 2.10-1.90 (m, 1H), 1.90-1.80 (m, 2H), 1.35-1.10 (m, 8H); LRMS (ESI), m/z 450 (M+H).

1. temperatureto warm to ambient temperature
2. concentrationThe mixture was then concentrated
3. customto give the crude product as a colorless oil
4. customThe crude product was purified by chromatography on a silica gel column
5. washeluted with 5:6 EtOAc/hexane