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

To a solution of 4-chloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 27, 2.5 g, 15.82 mmol) and methyl (3S,4R)-4-amino-3-methylpiperidine-1-carboxylate (Intermediate 37, 2.72 g, 15.82 mmol) in dichloromethane (200 mL) were added HOBt (2.42 g, 15.82 mmol) and N-methyl morpholine (5.2 mL, 47.46 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (5.43 g, 28.47 mmol) was added. The resulting reaction mixture was stirred at 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, dried over anhydrous sodium sulphate, filtered, concentrated under vacuum. Purification by column chromatography (silica, 35% ethylacetate in petroleum ether) afforded methyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidine-1-carboxylate 2.2 g (46%) as brown solid.

1. customThe resulting reaction mixture
2. stirringwas stirred at room temperature overnight
3. customThe reaction was quenched with the addition of 2N HCl (120 mL)
4. washThe organic layer was washed with sodium bicarbonate (150 mL), water (150 mL), and brine
5. dry with materialdried over anhydrous sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. customPurification by column chromatography (silica, 35% ethylacetate in petroleum ether)

ORD record

ord-7f82d0b87bc64def810e210c13303144

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071605B2