Sodium hydride → (R)-tert-butyl 3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

Participants

Reaction Steps

(R)-tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (7B) (9.95 mmol, 3.0 g) was added to a 200 mL round-bottomed flask equipped for stirring under nitrogen. DMF (50 mL) was added and the resultant solution was cooled to 0° C. with an ice bath. NaH (60% in mineral oil, 11.95 mmol, 0.478 g) was then added and the subsequent solution was allowed to stir under nitrogen for 0.5 hr. At this time 1-bromo-3-methoxypropane (12.44 mmol, 1.90 g) was added, the ice bath was removed and the reaction solution was allowed to warm to room temperature and stir fort hr. The reaction solution was then poured into ice-water, extracted with ethyl acetate, and washed once with saturated aqueous sodium chloride. The organic layer was collected and subsequently dried with anhydrous Na2SO4 and filtered. This filtrate was collected, concentrated, and dried in-vacuo affording a brown oil. This material was then purified by chromatography on silica gel (3-10% CH3OH in CH2Cl2) to afford (R)-tert-butyl 3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (7C) as a brown oil (9.63 mmol, 3.6 g, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.71 (br.s., 1H) 1.79-1.88 (br.s., 1H) 2.04-2.13 (m, 4H) 2.74-2.88 (br.s., 1H) 2.98-3.38 (m, 7H) 4.21-4.39 (m, 3H) 7.22-7.28 (m, 2H) 7.34-7.40 (dd, 1H, 6.57 Hz, 2.02 Hz) 7.72-7.77 (dd, 1H, 6.57 Hz, 2.02 Hz). ESI-MS: m/z 374.4 (M+H)+.

Provenance & Evidence