Isopropyl chloroformate → 1-Methylethyl 4-({[4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.23 mL, 1.30 mmol) was added to a suspension of 4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride (prepared as in Example 2, Step 1, 0.165 g, 0.43 mmol) in CH2Cl2 (10 mL). The mixture was cooled to 0° C. in an ice bath, and isopropyl chloroformate (1.0M in toluene, 0.48 mL, 0.48 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature, and stirred for 1.5 h, then diluted with ether, washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated. The crude product was purified by chromatography on a silica gel column eluted with 45 to 50% EtOAc/hexane to give 0.152 g (82%) of the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.97 (d, 2H, J=8.3 Hz), 7.83 (d, 2H, J=8.3 Hz), 7.64 (d, 2H, J=8.8 Hz), 7.04 (d, 2H, J=8.8 Hz), 4.90-4.80 (m, 1H), 4.20-4.10 (m, 2H), 3.90 (d, 2H, J=6.1 Hz), 3.13 (s, 3H), 2.95-2.75 (m, 2H), 2.10-1.95 (m, 1H), 1.90-1.80 (m, 2H), 1.35-1.20 (m, 8H); LRMS (ESI), m/z 432 (M+H).

Provenance & Evidence