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

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Reaction Steps

To a solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (WO2006087543. 2.8 g, 14.53 mmol) and methyl (3S,4R)-4-amino-3-methylpiperidine-1-carboxylate (Intermediate 37, 2.5 g, 14.53 mmol) in dichloromethane (200 mL) was added HOBT (2.22 g, 14.53 mmol) and N-methyl morpholine (4.82 mL, 43.60 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (5.12 g, 26.16 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 column chromatography (silica, 35% ethylacetate in pet ether) afforded methyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidine-1-carboxylate 3.4 g (67%) as brown solid.

Provenance & Evidence