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

Participants

Reaction Conditions

Reaction Steps

Into a 100 ml round bottomed flask with 4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (2.3 g, 5.53 mmol), tetrabutylammonium iodide (0.102 g, 0.276 mmol) was added 6N sodium hydroxide (13.82 ml, 83 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (1.378 ml, 11.05 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 on a silica gel cartridge and eluted with a gradient of 0% ethyl acetate/hexanes to 50% over 10 column volumes. The appropriate fractions were collected and evaporated to yield 4-(4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (911 mg, 1.873 mmol, 33.9% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.51 (s, 3H) 3.04-3.11 (m, 4H) 3.77-3.85 (m, 4H) 5.40 (s, 2H) 5.42-5.60 (m, 2H) 6.45 (d, J=2.02 Hz, 1H) 6.53 (d, 1H) 7.12 (t, J=7.83 Hz, 1H) 7.21 (d, J=2.02 Hz, 1H) 7.56 (d, J=7.83 Hz, 1H); LC/MS: MS (ES+) m/e 487 [M+H]+.

Provenance & Evidence