4-Methylmorpholine → HCID 59402508, compound

Participants

Reaction Steps

To a solution of 4-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 16, 1.01 g, 5.55 mmol) and ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate (Intermediate 24, 1.2 g, 5.55 mmol) in dichloromethane (480 mL) were added HOBt (850 mg, 5.55 mmol) and N-methyl morpholine (1.82 mL, 16.66 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (1.9 g, 9.99 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2N hydrochloric acid (120 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL) and brine, dried over anhydrous sodium sulphate, filtered, concentrated under vacuum. Purification by flash column chromatography (silica, 35% ethylacetate in pet ether) afforded ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate 1.5 g (71%) as solid.

Provenance & Evidence