Sodium hydride → 3-(2'-t-Butoxycarbonylbiphenyl-4-ylmethyl)-7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 476294Notes

Reaction equation

HRID 476294 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:16]=[C:15]([CH3:17])[C:8]2[N:9]=[C:10]([CH2:12][CH2:13][CH3:14])[NH:11][C:7]=2[CH:6]=1)=[O:4].[H-].[Na+].[C:20]([O:24][C:25]([C:27]1[C:28]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39]Br)=[CH:35][CH:34]=2)=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:16]=[C:15]([CH3:17])[C:8]2[N:9]=[C:10]([CH2:12][CH2:13][CH3:14])[N:11]([CH2:39][C:36]3[CH:37]=[CH:38][C:33]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])=[CH:34][CH:35]=3)[C:7]=2[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 9906257tert-Butyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 101308354-Methyl-2-propyl-1H-benzimidazole-6-carboxylic acid methyl ester

Product 1

HCID 687217563-(2'-t-Butoxycarbonylbiphenyl-4-ylmethyl)-7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid methyl esterYield 74.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid methyl ester (10.0 g, 43 mmol; prepared as described in Preparation 1) in DMF (300 mL) was cooled in an ice bath. Sodium hydride (4.5 g, 60 wt % in mineral oil) was slowly added over 5 minutes. 4′-Bromomethylbiphenyl-2-carboxylic acid t-butyl ester (15.7 g, 45.2 mmol; purchased from commercial source or prepared as described in Preparation 2) was then added. The mixture was gradually warmed to room temperature, then stirred at 75° C. overnight. The mixture was then cooled and concentrated in vacuo and the resultant residue was partitioned between saturated aqueous NaCl and EtOAc (1:1, 400 mL). The organic layer was collected, dried over MgSO4 and evaporated to dryness, yielding Intermediate (3a) as a pale yellow oil (16.0 g, 32.1 mmol). MS m/z: [M+H+] calcd for C31H34N2O4, 499.25. found 499.5.

Workup

  1. temperatureThe mixture was then cooled
  2. concentrationconcentrated in vacuo
  3. customthe resultant residue was partitioned between saturated aqueous NaCl and EtOAc (1:1, 400 mL)
  4. customThe organic layer was collected
  5. dry with materialdried over MgSO4
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-c5540af92e7747079268f6ce329ec19f
Source dataset
uspto-grants-2014_01
Patent number
US08637676B2

Reaction notes

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