Reaction #72790

Reaction equation

water

methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate

4-(chloromethyl)-1,2-dimethylbenzene

potassium carbonate

→

product

Yield 76.0%

methyl 1-[(3,4-dimethylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate

Yield 76.0%

Solvents

N,N-Dimethylformamide

Conditions

Workup

1. 1
   OtherThe resulting reaction mixture
2. 2
   TemperatureIt was cooled to room temperature
3. 3
   ExtractionThe mixture was extracted with EtOAc (50 mL×3)
4. 4
   WashThe combined organic phases were washed with brine (50 mL)
5. 5
   Concentrationconcentrated
6. 6
   OtherThe crude material was subjected to normal phase purification (0→40% EtOAc/Hexane)

Procedure

To a solution of methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate prepared as described in Example 26, step d (0.22 g, 0.799 mmol) in N,N-Dimethylformamide (DMF) (10 mL) was added in 4-(chloromethyl)-1,2-dimethylbenzene (0.185 g, 1.199 mmol) and potassium carbonate (0.331 g, 2.397 mmol). The resulting reaction mixture was stirred at 80° C. for 3 h. It was cooled to room temperature and poured into water (30 mL). The mixture was extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (50 mL) and concentrated. The crude material was subjected to normal phase purification (0→40% EtOAc/Hexane) then (0→1% MeOH/DCM) to give the product (0.24 g, 76%). MS (ES+) m/e 394.0 [M+H]+.

Source