Ammonia → tert-Butyl 4-carbamoyl-4-methylpiperidine-1-carboxylate

1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.284 g) was added to a mixture of 1-hyroxybenzotriazole hydrate (0.227 g) and 1-(tert-butoxycarbonyl)-4-methylpiperidine-4-carboxylic acid (0.300 g) in dichloromethane (6 mL). Diisopropylethylamine (0.644 mL) was added and the reaction was stirred overnight. Ammonia (7 mol/L; 5.28 mL) in methanol was syringed in and the reaction was stirred for 2 hours at room temperature. The volatiles were removed in vacuo. The residue was suspended in ethyl acetate (500 mL) and stirred for 15 minutes with a saturated ammonium chloride solution (250 mL). The layers were separated and the organic layer was washed with a saturated aqueous sodium bicarbonate solution (300 mL). The aqueous phase was extracted once with ethyl acetate (200 mL). The combined organics were dried with magnesium sulfate, and then concentrated to afford the title compound as a tan solid (0.299 g) with the following physical data.

1. stirringwas stirred for 2 hours at room temperature
2. customThe volatiles were removed in vacuo
3. stirringstirred for 15 minutes with a saturated ammonium chloride solution (250 mL)
4. customThe layers were separated
5. washthe organic layer was washed with a saturated aqueous sodium bicarbonate solution (300 mL)
6. extractionThe aqueous phase was extracted once with ethyl acetate (200 mL)
7. dry with materialThe combined organics were dried with magnesium sulfate
8. concentrationconcentrated

ORD record

ord-2738dde53c074559bc87d69cf5a6ddf3

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809538B2