Sodium Hydroxide → 4-(4-bromo-1-(3-chloro-2-methylbenzyl)-2-(fluoromethyl)-1H-benzo[d]imidazol-6-yl)morpholine

Participants

Reaction Conditions

Reaction Steps

Into a 100 ml round bottomed flask with 4-bromo-1-(3-chloro-2-methylbenzyl)-2-(fluoromethyl)-1H-benzo[d]imidazol-6-amine (2.49 g, 6.51 mmol), tetrabutylammonium iodide (0.120 g, 0.325 mmol) was added 6N sodium hydroxide (16.27 ml, 98 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (1.623 ml, 13.01 mmol), Reaction was heated to 110° C. for 2 h then cooled to room temperature and the mixture was extracted with EtOAc, washed with Brine and concentrated. The residue was purified by reversed phase eluted with a gradient of acetonitrile (0.1% TFA) and water (0.1% TFA v/v) (35-65%) over 12 minutes. The expected compound was collected and evaporated to yield a colorless oil 4-(4-bromo-1-(3-chloro-2-methylbenzyl)-2-(fluoromethyl)-1H-benzo[d]imidazol-6-yl)morpholine (777 mg, 1.716 mmol, 26.4% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.50 (s, 3H) 3.12-3.18 (m, 4H) 3.78-3.86 (m, 4H) 5.55-5.71 (m, 4H) 6.37 (d, J=8.08 Hz, 1H) 6.84 (d, J=2.02 Hz, 1H) 7.06 (t, J=8.08 Hz, 1H) 7.36 (d, J=8.08 Hz, 1H) 7.39 (d, 1H); LC/MS: MS (ES+) m/e 453 [M+H]+.

Provenance & Evidence