2-Bromo-4-trifluoromethylaniline → HCID 66884132, compound

Participants

Reaction Steps

A 4.5 L reactor was charged with 2-bromo-4-trifluoromethyl aniline (100 g), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (124 g, prepared as described in WO 2006/003494), 1,4-dioxane (2500 ml) and the solution was degassed for 30 minutes with argon. Dichloro-bis(triphenylphosphine)-palladium (5.6 g) was added and the resulting solution was stirred for 30 minutes at ambient temperature under an argon atmosphere. A degassed solution of sodium carbonate (127 g) in water (1200 ml) was added and the mixture was stirred at 60° C. for 3 hours. The mixture was cooled to ambient temperature and extracted with ethyl acetate (3×300 ml). The combined organic layers were washed with water (3×400 ml), brine then dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in heptane (200 ml) and cooled to −70° C. and then allowed to warm to 0° C. The solid was collected by filtration and rinsed with cold heptane to afford 4-(2-amino-5-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (128 g) as a brown solid. MS (ES+) 214/215; 243/244 (MH+-BOC); 287/288; 343 (MH+); 1H NMR (400 MHz, CDCl3) 1.5 (s, 9H), 2.4 (m, 2H), 3.65 (t, 2H), 4.05 (m, 2H), 5.8 (m, 1H), 6.7 (d, 1H), 7.2 (d, 1H), 7.3 (dd, 1H).

Provenance & Evidence