Triethylamine → HCID 86706868, compound

Participants

Reaction Steps

Isobutyl chloroformate (1.1 mL, 8.6 mmol) was added to a solution of 2-{[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}-6-(trifluoromethyl)isonicotinic acid (2.8 g, 7.2 mmol, from Step 2) and triethylamine (2.0 mL, 14 mmol) in tetrahydrofuran (30. mL) at 0° C. After stirring for 30 minutes, the reaction mixture was filtered through a short pad of celite into a flask containing a mixture of sodium tetrahydroborate (0.95 g, 25 mmol) in water (15 mL) at 0° C. The celite pad was rinsed with three portions of THF (3×30 mL) into the reaction flask. The reaction was allowed to warm to room temperature and stir for 1 hour. The reaction mixture was recooled in an ice bath and was quenched by the addition of saturated ammonium chloride solution. The product was extracted with a 150 mL portion of ethyl acetate. The organic layer was washed with water and brine, was dried over sodium sulfate, filtered and concentrated. Flash chromatography, using a 120 g silica gel cartridge and eluting with a gradient from 0-80% EtOAc in hexanes afforded product as a white solid (2.7 g, 100%). 1H NMR (400 MHz, CDCl3) δ 6.87 (s, 1H), 6.56 (s, 1H), 5.02-4.36 (m, 2H), 4.09-3.94 (m, 2H), 3.81 (dtt, J=14.2, 8.0, 3.9 Hz, 1H), 3.03-2.85 (m, 2H), 2.07-1.97 (m, 2H), 1.46 (s, 9H), 1.37 (qd, J=12.2, 3.8 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ −69.21 (s). LCMS (M+Na)+: 398.0.

Provenance & Evidence