Dimethyl Sulfoxide → 4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

In a 22 L 3 neck round bottom flask equipped with a mechanical stirrer, nitrogen inlet, drying tube and thermocouple charge DMSO (1385 mL) and 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (206.71 g, 0.5 mol, 1 eq). Heat the resulting suspension to 43-48° C. then add sodium hydroxide powder (50 g, 1.25 mol, 2.5 eq) in one portion. Stir the resulting suspension for 1 hour at 43-48° C. To this suspension add 2-chloro-N,N-dimethylethanamine hydrochloride (90 g, 0.625 mol, 1.25 eq). Stir the resulting suspension for 35-40 minutes. Cool the reaction mixture to 18-23° C. and add cold water (227.4 mL). Once water addition is complete, bring the reaction mixture temperature to 20-25° C., stir for 60-90 minutes and filter the suspension. Wash the solids with a mixture of DMSO (103.4 mL) and water (51.7 mL) two times. Wash the solids with water (2×517 mL) and dry solids on a filter with suction to afford the target compound (219.9 g, 87.5% yield) as a tan solid. 1H NMR (300 MHz, DMSO): 8.04-8.00 (m, 2H), 7.74 (s, 1H), 7.46 (t, J=9.9 Hz, 1H), 4.06-3.99 (m, 4H), 3.03-2.93 (m, 3H), 2.57 (t, J=6.3 Hz, 2H), 2.19 (s, 6H), 1.81-1.77 (m, 2H), 1.70-1.55 (m, 2H), 1.42 (s, 9H).

Provenance & Evidence