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

To a solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (WO2006087543, 1.77 g, 9.13 mmol) and ethyl (3S,4R)-4-amino-3-propoxypiperidine-1-carboxylate (see Intermediate 73, 2.1 g, 9.13 mmol) in dichloromethane (150 mL) was added N-Hydroxybenzotriazole (1.67 g, 10.95 mmol) and N-methylmorpholine (2.76 g, 27.39 mmol). The reaction mixture was stirred for 1 h at room temperature and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.023 g, 16.43 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2N hydrochloric acid (30 mL) and the layers were separated. The organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively, and dried over anhydrous sodium sulphate, filtered, and concentrated under vacuum to afford ethyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate 3.3 g (89.1%) as solid.

1. customThe resulting reaction mixture
2. stirringwas stirred at room temperature overnight
3. customThe reaction mixture was quenched with 2N hydrochloric acid (30 mL)
4. customthe layers were separated
5. washThe organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively
6. dry with materialdried over anhydrous sodium sulphate
7. filtrationfiltered
8. concentrationconcentrated under vacuum

ORD record

ord-e766c8a8aeff454a844d7bf48beb91c1

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071605B2