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

Temperature

0 °C

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).

1. temperatureto warm to ambient temperature
2. washwashed with water and brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationthe filtrate was concentrated
6. customThe crude product was purified by chromatography on a silica gel column
7. washeluted with 45 to 50% EtOAc/hexane

ORD record

ord-07827ac58af245d78ec860be7dc5eb73

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101634B2