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

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Reaction Steps

4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (3.42 g, 8.06 mmol) was stirred in 6M sodium hydroxide (70 mL, 420 mmol) solution with 1-bromo-2-(2-bromoethoxy)ethane (5.03 mL, 40.3 mmol) and tetrabutylammonium iodide (0.298 g, 0.806 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 Et2O/EtOAc. The organic was washed with H2O and brine and dried over MgSO4 and concentrated to leave a thick dark residue containing the desired product. The desired product was dissolved in CHCl3, loaded onto a silica column, and was purified by flash chromatography eluting with EtOAc/Hex 20% to 40% over 20 column volumes. The fractions containing the desired compound by TLC were combined and concentrated and the resultant dark oil was triturated with Et2O/Hexanes to provide 4-(4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (1.62 g, 3.28 mmol, 40.7% yield) as a light orange solid. MS (ES+) m/e: 495.1, 495.8 [M+H]+

Provenance & Evidence