Isopropyl chloroformate → HCID 57619803, compound

HRID 1642498Notes

Reaction equation

HRID 1642498 reaction equation
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@@H:22]4[C@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]4)[CH2:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH2:24](N(CC)CC)C.Cl[C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33]>ClCCl.[OH-].[Na+]>[O:23]=[C:15]1[CH2:16][C@@H:17]2[C@H:22]([CH2:21][CH2:20][CH2:19][CH2:18]2)[N:14]1[CH:11]1[CH2:12][CH2:13][N:8]([C:2]2([CH3:1])[CH2:3][CH2:4][N:5]([C:32]([O:34][C:35]([CH3:37])([CH3:24])[CH3:36])=[O:33])[CH2:6][CH2:7]2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 57619825HCID 57619825, compound

Product 1

HCID 57619803HCID 57619803, compoundYield 49.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

A solution of (3aR,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-indol-2-one (100 mg, 0.31 mmol) and triethylamine (0.044 mL, 0.31 mmol) in dichloromethane (5 mL) was added with isopropyl chloroformate (0.313 mL, 1M solution in toluene, 0.31 mmol) dropwise at 0° C. and stirred for 2 hours. Diluted with dichloromethane (60 mL) and 1 N NaOH (10 mL) was added. The phases were separated and aqueous phase was extracted with dichloromethane (2×15 mL). The combined organic phases were washed with brine, concentrated in vacuo and the residue was purified by preparative LC/MS (high pH) to provide the title compound (63 mg, 49.6%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.85 (s, 3H), 1.19 (d, J=6.25 Hz, 6H), 1.21-1.43 (m, 6H), 1.48-1.87 (m, 10H), 1.87-2.00 (m, 1H), 2.04-2.18 (m, 2H), 2.28 (d, J=6.64 Hz, 1H), 2.32 (d, J=7.03 Hz, 1H), 2.88 (t, J=12.70 Hz, 2H), 2.97 (t, J=8.59 Hz, 1H), 3.20-3.35 (m, 2H), 3.39-3.58 (m, 2H), 3.90 (t, J=12.30 Hz, 1H), 4.76-4.93 (m, 1H). MS (M+1): 406.2.

Workup

  1. additionwas added
  2. customThe phases were separated
  3. extractionaqueous phase was extracted with dichloromethane (2×15 mL)
  4. washThe combined organic phases were washed with brine
  5. concentrationconcentrated in vacuo
  6. customthe residue was purified by preparative LC/MS (high pH)

Sources & evidence

ORD record
ord-951485b9735446708ee954da347f4d5f
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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