2,6-Dichloropyridine → N-(6-chloropyridin-2-yl)-N,3-dimethylbenzenesulfonamide

Participants

Reaction Steps

N,3-dimethylbenzenesulfonamide (0.250 g, 1.3 mmol) was added to a microwave vial, equipped with a stir bar. Then DMF (3 ml) was added to the mixture, followed by sodium hydride (0.160 g, 6.7 mmol) and allowed the mixture to stir 20 minutes. Then 2,6-dichloropyridine (0.300 g, 2.0 mmol), palladium(II) acetate (0.030 g, 0.13 mmol) and Xantphos (0.024 g) was added to the mixture. The vial was capped and placed into CEM Microwave for 10 minutes at 100° C., while 100 watts of energy was supplied via Powermax® (Simultaneous heating while cooling technology). The reaction was monitored by LC/MS, which showed desired product in the mixture. The mixture was diluted with DCM and saturated sodium bicarbonate solution. The organic layer was extracted with 4:1 DCM/MeOH (3×25 ml). Combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by ISCO silica-gel chromatography on a 40 gram column, in a gradient of 1-10% EtOAc/Hexanes over 30 minutes. The fractions with desired product were combined and concentrated to give N-(6-chloropyridin-2-yl)-N,3-dimethylbenzenesulfonamide (0.205 g, 51% yield) as a colorless oil. MS (ESI pos. ion) m/z: 297 (MH+). Calc'd exact mass for C13H13ClN2O2S: 296. 1H NMR (400 MHz, chloroform-d): 2.38 (d, J=2.01 Hz, 3H), 3.31 (d, J=2.51 Hz, 3H), 7.11 (d, J=3.51 Hz, 1H), 7.26-7.48 (m, 4H), 7.57-7.67 (m, 2H).

Provenance & Evidence