4-Methylmorpholine → (R)-2-(benzo[1,3]dioxol-5-yloxy)-N-[4-(1-carbamoyl-ethoxy)-2-fluoro-benzyl]-nicotinamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (R)-2-[4-({[2-(benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-3-fluoro-phenoxy]-propionic acid (0.25 g, 0.55 mmol) in ethylene glycol dimethyl ether (20 mL) at −10° C. was added N-methyl morpholine (0.06 mL, 0.55 mmol) followed by dropwise addition of isobutyl chloroformate (0.071 mL, 0.55 mmol). The turbid solution was stirred at −10° C. 10 min. Ammonia gas was bubbled through the reaction mixture 10 min, which was then warmed to room temperature and stirred a further 15 min. The reaction mixture was partitioned between chloroform and water. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford a white solid. Flash column chromatography (1% methanol/dichloromethane) yielded 0.15 g of a white solid (60% yield).

Provenance & Evidence