Reaction #1583895

Reaction equation

4-Bromomethyl-2-fluorobenzoic acid methyl ester

(7-Methyl-2-propyl-3H-benzoimidazol-5-yl)methanol

sodium hydride

→

Intermediate ( 8a )

Yield 43.2%

2-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl ester

Yield 43.2%

Solvents

DMF

DMF

Conditions

Workup

1. 1
   Temperaturethe mixture was warmed to room temperature
2. 2
   workup.STIRRINGstirred for 10 minutes
3. 3
   OtherThe solution was partitioned between EtOAc (300 mL) and 150 mL 10% LiCl (aqueous)
4. 4
   OtherThe organic layer was separated
5. 5
   Dryingdried over MgSO4
6. 6
   Concentrationconcentrated
7. 7
   Otherchromatographed

Procedure

(7-Methyl-2-propyl-3H-benzoimidazol-5-yl)methanol (3 g, 15 mmol; prepared as described in Preparation 7) was dissolved in 20 mL of dry DMF. The solution was cooled to 0° C. and sodium hydride (598 mg, 15 mmol, 60 wt % in mineral oil) was added. The mixture was stirred for 30 minutes. 4-Bromomethyl-2-fluorobenzoic acid methyl ester (3.7 g, 15 mmol; prepared as described in Preparation 3) in 50 mL of DMF was added, and the mixture was warmed to room temperature and stirred for 10 minutes. The solution was partitioned between EtOAc (300 mL) and 150 mL 10% LiCl (aqueous). The organic layer was separated, dried over MgSO4 and concentrated. The concentrate was flash chromatographed to produce Intermediate (8a) as a clear oil (2.4 g). MS m/z: [M+H+] calcd for C21H23FN2O3, 371.7. found 371.0.

Source