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

HRID 1992084Notes

Reaction equation

HRID 1992084 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:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[CH2:22][CH2:21][N:20]([CH:23]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:24]([OH:26])=[O:25])[CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[N:3]=1.[CH3:43][Si](C=[N+]=[N-])(C)C>CO>[CH3:43][O:25][C:24](=[O:26])[CH:23]([N:20]1[CH2:21][CH2:22][C:17]([CH2:16][CH2:15][N:14]2[CH:12]3[CH2:11][CH2:10][CH:9]2[CH2:8][CH:7]([N:6]2[C:5]4[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=4[N:3]=[C:2]2[CH3:1])[CH2:13]3)([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:18][CH2:19]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 56674000(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)(phenyl)acetic acid

Product 1

HCID 56663741methyl (4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)(phenyl)acetateYield 81%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of (4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo-[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)(phenyl)acetic acid (prepared above) (12 mg, 0.02 mmol) in methanol (2 mL) was added (trimethylsilyl)diazomethane (100 μL, 2.0 M in hexans). The reaction mixture was stirred for 30 minutes at room temperature. After evaporation of the solvents, the residue was purified by flash chromatography, eluting with a gradient of 0-10% methanol in ethyl acetate, to afford an oil (10 mg, 81%) as methyl(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)(phenyl)acetate. 1H NMR (300 MHz, CDCl3) δ 7.67 (d, J=7.1 Hz, 1H), 7.45-7.42 (m, 2H), 7.37-7.27 (m, 8H), 7.23-7.15 (m, 3H), 4.61 (m, 1H), 3.89 (s, 1H), 3.67 (s, 3H), 3.25-3.24 (m, 2H), 2.72-2.70 (m, 1H), 2.55 (s, 4H), 2.42-2.16 (m, 6H), 2.03-1.85 (m, 7H), 1.81-1.76 (m, 3H), 1.61-1.58 (m, 2H). HRMS m/z (M+H)+ calcd: 577.3543, obsd: 577.3557.

Workup

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

Sources & evidence

ORD record
ord-132bf65f01b24bc3bef900bd26aebe1c
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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