Triethylamine → HCID 86712657, compound

Participants

Reaction Conditions

Reaction Steps

Zinc(II) chloride (1.0 M in Et2O; 0.661 mL, 0.661 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.132 g, 0.606 mmol) in 1:1 DCE/t-BuOH (5 mL) at 0° C. under nitrogen. The resulting mixture was stirred for 1 hour at 0° C. then tert-butyl 4-(4-amino-2-methylphenyl)piperidine-1-carboxylate (A39) (0.160 g, 0.551 mmol) in 1:1 DCE/t-BuOH (5 mL) was added. A solution of Et3N (840 μL, 0.606 mmol) in 1:1 DCE/t-BuOH (5 mL) at 0° C. was then added and the resulting mixture was vigorously stirred for a further 30 minutes at 0° C. then at room temperature for 16 hours. The volatiles were removed in vacuo to afford a brown residue which was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to yield a pale yellow solid. The solid was suspended in MeOH (10 mL) and water (10 mL) and the resulting suspension filtered to give the title compound A40 as a white solid (0.231 g, 89%); 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 7.35 (d, J=8.2 Hz, 1H), 7.27 (brs, 1H), 7.24 (d, J=2.3 Hz, 1H), 7.11 (d, J=8.4 Hz, 1H), 4.32-4.04 (m, 2H), 2.79-2.73 (m, 3H), 2.30 (s, 3H), 1.67 (d, J=13.0 Hz, 2H), 1.62-1.45 (m, obscured), 1.42 (s, 9H). LCMS-A: rt 6.895 min; m/z 469.1 [M−H]−.

Provenance & Evidence