Diisopropylethylamine → Isopropyl 2-(5-bromo-4-(4-methoxy-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-methoxy-4-methylpiperidine, HCl (1.0 g, 6.04 mmol) and DIEA (4.2 mL, 24.5 mmol) in anhydrous CH3CN (30 mL) was added isopropyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (3.4 g, 6.04 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80° C.) and stirred for 24 h; cooled, diluted with ether, washed with water, brine, and dried (MgSO4). The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient eluted (5-35% EtOAc/hexanes) using an Isolera chromatography station gave isopropyl 2-(5-bromo-4-(4-methoxy-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate 1.57 g (61%). 1H NMR (500 MHz, DMSO-d6) δ 5.08-5.03 (m, 1H), 3.44-3.40 (m, 4H), 3.11 (s, 3H), 2.60 (s, 3H), 2.29 (s, 3H), 1.67 (d, J=13.2 Hz, 2H), 1.43 (br. s., 2H), 1.29 (d, J=6.2 Hz, 6H), 1.11 (s, 3H). UPLC (M+H)=429.3.

Provenance & Evidence