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

HRID 423457Notes

Reaction equation

HRID 423457 reaction equation
C(N(C(C)C)CC)(C)C.Cl.[CH3:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH2:28][CH:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)(=[O:14])=[O:13].Cl[C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37]>C(Cl)Cl.CCOCC>[CH3:11][S:12]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH2:28][CH:29]3[CH2:34][CH2:33][N:32]([C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37])[CH2:31][CH2:30]3)=[CH:23][CH:22]=2)=[CH:19][CH:20]=1)(=[O:14])=[O:13]

Participants

6

Reactant 3

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 666725844-({[4'-(Methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride

Product 1

HCID 591777521-Methylethyl 4-({[4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-07827ac58af245d78ec860be7dc5eb73
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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