Reaction #1583891

Reaction equation

7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid methyl ester

Sodium hydride

4′-Bromomethylbiphenyl-2-carboxylic acid t-butyl ester

→

Intermediate ( 3a )

Yield 74.7%

3-(2′-t-Butoxycarbonylbiphenyl-4-ylmethyl)-7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid methyl ester

Yield 74.7%

Solvents

DMF

Conditions

Workup

1. 1
   TemperatureThe mixture was then cooled
2. 2
   Concentrationconcentrated in vacuo
3. 3
   Otherthe resultant residue was partitioned between saturated aqueous NaCl and EtOAc (1:1, 400 mL)
4. 4
   OtherThe organic layer was collected
5. 5
   Dryingdried over MgSO4
6. 6
   Otherevaporated to dryness

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.

Source