Benzoyl chloride → [4-[2-[(1R,5S)-3-(2-methylbenzimidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]ethyl]-4-phenyl-1-piperidyl]-phenyl-methanone

HRID 1992060Notes

Reaction equation

HRID 1992060 reaction equation
Cl.Cl.[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][CH:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1.C(N(CC)CC)C.[C:42](Cl)(=[O:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>ClCCl>[C:42]([N:22]1[CH2:21][CH2:20][C:19]([CH2:18][CH2:17][N:16]2[C@H:14]3[CH2:13][CH2:12][C@@H:11]2[CH2:10][CH:9]([N:8]2[C:7]4[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=4[N:5]=[C:4]2[CH3:3])[CH2:15]3)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:24][CH2:23]1)(=[O:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 686757782-methyl-1-{8-[2-(4-phenyl piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride

Product 1

HCID 25132254[4-[2-[(1R,5S)-3-(2-methylbenzimidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]ethyl]-4-phenyl-1-piperidyl]-phenyl-methanoneYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of endo 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride II (0.53 g, 1.06 mmol) in dichloromethane (10 mL) and triethylamine (0.32 g, 3.18 mmol) was added benzoyl chloride (0.156 g, 1.11 mmol) at 0° C. The ice bath was then removed and the mixture allowed to stir for 30 min. The solvents were then removed in vacuo and the resulting solid was partitioned between ethyl acetate and water (3×). The organic layer was dried with magnesium sulfate and the solvent removed in vacuo, yielding crude 17, which was them purified using the supercritical fluid chromatography, resulting in 525 mg of pure 1-{(1R,5S)-8-[2-(1-benzoyl-4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-methyl-1H-benzimidazole 17 (yield 93%). 1H NMR (400 MHz, CDCl3) δ 7.20 (1H, m), 6.94 (7H, m), 6.82 (4H, m), 6.70 (2H, m), 4.15 (1H, m), 3.75 (1H, m), 3.11 (1H, m), 2.98 (4H, m), 2.93 (1H, m), 2.78 (3H, m), 2.05 (3H, s), 2.04 (2H, m), 1.88 (3H, m), 1.70 (1H, m), 1.59-1.24 (4H, m), 1.14 (2H, m). HRMS m/z (M+H)+Calc 533.3280; (M+H)+Obs 533.3300.

Workup

  1. customThe ice bath was then removed
  2. customThe solvents were then removed in vacuo
  3. customthe resulting solid was partitioned between ethyl acetate and water (3×)
  4. dry with materialThe organic layer was dried with magnesium sulfate
  5. customthe solvent removed in vacuo
  6. customyielding crude 17, which
  7. custompurified

Sources & evidence

ORD record
ord-82c8049feec44d7fa3f5d06e581e50c3
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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