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

Participants

Reaction Conditions

Reaction Steps

Into a 100 ml round bottomed flask charged with 4-bromo-1-(3-chloro-2-methylbenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine (3.1 g, 7.40 mmol) and tetrabutylammonium iodide (0.137 g, 0.370 mmol) was added 6N sodium hydroxide (18.51 ml, 111 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (1.87 ml, 14.81 mmol). The reaction was heated to 110° C. and was monitored by LCMS. The reaction was complete after 2 h. The reaction was cooled to RT and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic phase was washed with brine (30 mL), the organic extracts were combined, concentrated in vacuo, and the residue was purified by flash chromatography on silica gel eluted with a solution of (2N ammonia in methanol)/chloroform (0% to 10%). The fractions containing product were combined, then concentrated in vacuo to provide the desired product (1.62 g, 3.31 mmol, 44.8% yield) as a brown solid. NMR & LCMS were consistent with the structure. MS (ES+) m/e: 487.1, 488.1 [M+H]+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.42 (s, 3H) 3.03-3.21 (m, 4H) 3.78-3.89 (m, 4H) 5.43 (s, 2H) 6.28 (d, J=7.58 Hz, 1H) 6.38 (d, J=2.02 Hz, 1H) 6.99 (t, J=7.96 Hz, 1H) 7.29 (d, J=2.27 Hz, 1H) 7.34 (d, J=7.83 Hz, 1H)

Provenance & Evidence