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

Participants

Reaction Steps

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 1.00 g, 2.654 mmol) in dichloroethane (2.6 ml) and DMF (1 drop) was added oxalyl chloride (0.2778 ml, 3.185 mmol), and the reaction was stirred at ambient temperature for 2 hours. The reaction was diluted with pyridine (10 ml), and 6-bromopyridin-2-amine (0.9183 g, 5.308 mmol) was added. The reaction was heated to 80° C. for 16 hours, then cooled to ambient temperature and diluted with EtOAc. The reaction was washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified on silica gel eluting with a linear gradient of 5-70% EtOAc/hexanes to yield the desired compound (1.2 g, 2.257 mmol, 85.02% yield).

Provenance & Evidence