Dimethylformamide → 6-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

Participants

Reaction Steps

To a suspension of 6-chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid (33.7 g, 99.5 mmol) in dichloromethane (500 mL) at 0° C. was added DIPEA (17.1 mL, 99.5 mmol). The reaction mixture was stirred for 10 minutes, then DMF (2 mL) and oxalyl chloride (8.7 mL, 99.5 mmol) were added dropwise (CAUTION: EFFERVESCENCE). The reaction mixture was stirred at room temperature for 2 hours and then added dropwise to a solution of DIPEA (17.1 mL, 99.5 mmol) in MeOH (500 mL) at 0° C. over a 45 minutes period. The reaction mixture was stirred at room temperature for 18 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate, followed by water, then brine, dried (Na2SO4), filtered and evaporated in vacuo to afford the title compound as a brown foam which was used without purification into the next step (36.4 g). LCMS (method B) RT=5.35 min, M+H+=353.

Provenance & Evidence