Oxalyl chloride → Ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 1.0 g, 2.65 mmol) was diluted with dichloromethane (10 mL) followed by the addition of oxalyl chloride in dichloromethane (2M) (1.46 mL, 2.92 mmol) and DMF (1 drop). After stirring for 20 minutes, 6-bromopyridin-2-amine (0.505 g, 2.92 mmol) and diisopropyl ethylamine (1.16 ml, 6.64 mmol) were added and the reaction was stirred overnight at ambient temperature, then heated to 70° C. for 4 hours. The reaction mixture was cooled, then loaded directly onto a Biotage 40 cartridge, eluting with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes to yield ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (500 mg, 0.940 mmol, 35.4% yield).

Provenance & Evidence