Isopropyl chloroformate → 1-Methylethyl 4-({[2'-fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate

HRID 423500Notes

Reaction equation

HRID 423500 reaction equation
C(N(C(C)C)CC)(C)C.Cl.[F:11][C:12]1[CH:17]=[C:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:15]=[CH:14][C:13]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:24][CH:23]=1.Cl[C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38]>C(Cl)Cl>[F:11][C:12]1[CH:17]=[C:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:15]=[CH:14][C:13]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38])[CH2:32][CH2:31]2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 666734284-({[2'-Fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride

Product 1

HCID 249940291-Methylethyl 4-({[2'-fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-2ce4be78b7bb4eefbbff4ccde71f3a03
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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