4-Methylmorpholine → ethyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate

Participants

Reaction Steps

To a solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (WO200687543, 1.18 g, 6.15 mmol) and ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate (Intermediate 24, 1.33 g, 6.15 mmol) in dichloromethane (170 mL) were added HOBT (941 mg, 6.15 mmol) and N-methyl morpholine (2.02 mL, 18.45 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (2.11 g, 11.07 mmol) was added. The resulting reaction mixture was stirred for room temperature overnight. The reaction was quenched with the addition of 2N HCl (120 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL), and brine, and 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-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate 1.9 g (49%) as solid.

Provenance & Evidence