Reaction #72782

Reaction equation

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

1-(bromomethyl)naphthalene

K2CO3

→

desired product

Yield 74.0%

methyl 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxylate

Yield 74.0%

Solvents

water

Conditions

Workup

1. 1
   Temperaturethe mixture was cooled to room temperature
2. 2
   ExtractionIt was extracted with EtOAc (500 mL×3)
3. 3
   Washthe combined organic layers were washed with brine (500 mL×3)
4. 4
   Concentrationconcentrated in-vacuo
5. 5
   OtherThe residue was purified by silica gel chromatography
6. 6
   Washeluted with MeOH

Procedure

A mixture of methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate (4.125 g), 1-(bromomethyl)naphthalene (5 g) and K2CO3 (6.2 g) was stirred at 80° C. for 3 h. When TLC showed no starting material remaining, the mixture was cooled to room temperature and then poured into water (500 mL). It was extracted with EtOAc (500 mL×3) and the combined organic layers were washed with brine (500 mL×3) and then concentrated in-vacuo. The residue was purified by silica gel chromatography eluted with MeOH:DCM=1:100 to afford the desired product as a yellow solid (4.6 g, 74%). 1H NMR (300 MHz, DMSO-d6): δ ppm 2.42 (s, 3H), 3.04 (t, 4H, J=4.8 Hz), 3.68 (t, 4H, J=4.8 Hz), 3.90 (s, 3H,), 6.02 (s, 1H), 6.28 (d, 1H, J=7.5 Hz), 7.29 (d, 1H, J=2.4 Hz), 7.32 (d, 1H, J=7.5 Hz), 7.39 (d, 1H, J=2.4), 7.60-7.71 (m, 2H), 7.84 (d, 1H, J=8.4 Hz), 8.01 (d, 1H, J=7.5 Hz), 8.24 (d, 1H, J=7.5 Hz); LC-MS: m/e=416 [M+1]+.

Source