Trimethylsilyldiazomethane → methyl 2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoate

HRID 1992053Notes

Reaction equation

HRID 1992053 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]2[CH2:13][CH:12]3[N:14]([CH2:15][CH2:16][C:17]4([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[CH2:22][CH2:21][N:20]([C:23]([C:25]5[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=5[C:27]([OH:29])=[O:28])=[O:24])[CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:40]=[CH:41][CH:42]=[CH:43][C:4]=2[N:3]=1.[CH3:44][Si](C=[N+]=[N-])(C)C>CO>[CH3:1][C:2]1[N:6]([CH:7]2[CH2:13][CH:12]3[N:14]([CH2:15][CH2:16][C:17]4([C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=5)[CH2:22][CH2:21][N:20]([C:23]([C:25]5[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=5[C:27]([O:29][CH3:44])=[O:28])=[O:24])[CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:40]=[CH:41][CH:42]=[CH:43][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 545850052-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoic acid

Product 1

HCID 58728091methyl 2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoic acid 8 (40 mg, 0.07 mmol) in methanol (2 mL) was added (trimethylsilyl)diazomethane (0.35 mL, 2.0 M in hexanes). The resulting mixture was further stirred for 30 minutes. After evaporation of solvents, the residue was purified by flash chromatography on silical gel, eluting with a gradient of 0-10% methanol in ethyl acetate to afford methyl 2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoate 9 as an oil (40 mg, quant.). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=7.6 Hz, 1H), 7.64 (d, J=7.7 Hz, 1H), 7.54 (s, 1H), 7.45-7.41 (m, 1H), 7.37-7.34 (m, 2), 7.29-7.21 (m, 5H), 7.18-7.10 (m, 2H), 4.63-4.53 (m, 1H), 4.21-4.18 (m, 1H), 3.86 (br, 3H), 3.44 (br, 1H), 3.24 (br, 3H), 3.08 (br, 1H), 2.53 (s, 3H), 2.36-2.34 (m, 3H), 1.91-1.71 (m, 11H), 1.59 (d, J=7.0 Hz, 2H). HRMS m/z (M+H)+ calcd 591.3335; obsd 591.3353.

Workup

  1. customAfter evaporation of solvents
  2. customthe residue was purified by flash chromatography on silical gel
  3. washeluting with a gradient of 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-b626a32e4aab4ace96b79972e90fc9a2
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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