Toluene → 1-(4-Chlorophenyl)-N-methoxy-N-methylpiperidine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A flask containing 2-(2′-di-tent-butylphosphine)biphenylpalladium(II) acetate (0.927 g, 2.003 mmol) and potassium tert-butoxide (1.798 g, 16.03 mmol) was flushed with nitrogen and then charged with 4-bromochlorobenzene (3.07 g, 16.03 mmol), N-methoxy-N-methylpiperidine-4-carboxamide (2.3 g, 13.35 mmol) and anhydrous toluene (25 mL). The resulting mixture was stirred under nitrogen at 100° C. for 1.5 h. After this time, the reaction mixture was cooled to room temperature, diluted with ether (200 mL), washed with water and brine, dried over MgSO4 and concentrated to yield a residue. The residue was purified by flash chromatography using a 120 g silica gel cartridge and an eluent gradient from 10:1 Hex/EtOAc to 2:1 EtOAc/Hex. The fractions containing the product were pooled and concentrated on a rotary evaporator to the title compound (2.2 g, 7.78 mmol, 58.3% yield) as a yellow-green solid. LC-MS: (Waters Sunfire C18 4.6 mm×50 mm). 283.19, [M+H]; tR=1.79 min; 4 min gradient from 10/90/0.1 MeOH/H2O/TFA to 90/10/0.1 MeOH/H2O/TFA at 4 mL/min flow rate. 1H NMR (400 MHz, CDCl3) δ ppm 7.13-7.21 (2H, m), 6.81-6.87 (2H, m), 3.72 (3H, s), 3.69 (1H, t, J=3.30 Hz), 3.66 (1H, t, J=2.86 Hz), 3.19 (3H, s), 2.70-2.82 (3H, m), 1.82-1.94 (4H, m).

Provenance & Evidence