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

Participants

Reaction Steps

The crude product from the previous reaction 4-bromo-1-(3-chloro-2-methylbenzyl)-2-(difluoromethyl)-1H-benzo[d]imidazol-6-amine (2.25 g, 5.62 mmol) was stirred in 6M sodium hydroxide (30 mL, 180 mmol) solution with 1-bromo-2-(2-bromoethoxy)ethane (1.5 mL, 12.03 mmol) and tetrabutylammonium iodide (0.207 g, 0.562 mmol) at 110° C. After stirring for 2.5 hr the mixture was cooled and the aqueous was decanted and the remaining sticky solid was dissolved in EtOAc. The organic was washed with H2O and brine, and dried over MgSO4 and concentrated to leave a residue that was purified by column chromatography. The residue was loaded onto a 25 g Silica column and eluted with EtOAc/Hex 10% to 40% over 15 minutes. The cleanest fractions containing desired product were combined and concentrated in-vacuo to afford 892 mg (34% yield) of the titled compound. LC/MS: MS (ES+) m/e 471.8 [M+H]+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.22-7.37 (m, 3H), 6.81-7.14 (m, 2H), 6.31-6.42 (m, 2H), 5.51 (s, 2H), 3.76-3.89 (m, 4H), 3.03-3.20 (m, 4H), 2.48 (s, 3H)

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