Potassium Carbonate → But-2-ynyl 4-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzimidazol-1-yl]-1-piperidyl]-4-methyl-piperidine-1-carboxylate

HRID 1642500Notes

Reaction equation

HRID 1642500 reaction equation
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@H:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]4[NH:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Cl[C:31]([O:33][CH2:34][C:35]#[C:36][CH3:37])=[O:32]>O.ClCCl>[O:23]=[C:15]1[N:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:2]3([CH3:1])[CH2:7][CH2:6][N:5]([C:31]([O:33][CH2:34][C:35]#[C:36][CH3:37])=[O:32])[CH2:4][CH2:3]3)[CH2:9][CH2:10]2)[C@H:18]2[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]2[NH:16]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 41316692-Butyn-1-yl chloroformateHCID 57619802(3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

Product 1

HCID 25221447But-2-ynyl 4-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzimidazol-1-yl]-1-piperidyl]-4-methyl-piperidine-1-carboxylateYield 7.59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (3aS,7aS)-3-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-1H-benzimidazol-2-one (HCl salt, 0.4105 g, 1.15 mmol) and potassium carbonate (0.170 g, 1.23 mmol) in water (3.00 mL) was added a solution of but-2-ynyl chloroformate (0.156 mL, 1.38 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at room temperature overnight. The mixture was poured into hydrometrix varian column chem elut catridge column and rinsed with dichloromethane (3 Column volumes). Concentrated in vacuo and the residue was purified by flash chromatography (0 to 50% MeOH/Ethyl acetate) and followed by preparative LC/MS (high pH) to give the title compound (0.036 g, 7.59%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1H NMR (400 MHz, CDCl3) δ ppm 1.30-1.47 (m, 6H), 1.49 (s, 2H), 1.62-1.76 (m, 1H), 1.76-2.00 (m, 9H), 2.34 (s, 2H), 2.72-2.98 (m, 6H), 2.99-3.09 (m, 2H), 3.49-3.85 (m, 2H), 4.11 (s, 1H), 4.27 (s, 2H), 4.49 (s, 1H), 4.61-4.72 (m, 2H) MS (M+1): 417.3.

Workup

  1. additionThe mixture was poured into hydrometrix varian column chem elut catridge column
  2. washrinsed with dichloromethane (3 Column volumes)
  3. concentrationConcentrated in vacuo
  4. customthe residue was purified by flash chromatography (0 to 50% MeOH/Ethyl acetate)

Sources & evidence

ORD record
ord-ae3371726be84aecaae6f1cc7b2d718c
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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