Dimethylamine → 1-BOC-4-DIMETHYLCARBAMOYLPIPERIDINE

Temperature

0 °C

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid (8.0 g, 35 mmol) was dissolved in dichloromethane (70 ml) and N,N-dimethylformamide (35 ml). 1-Hydroxy-7-azabenzotriazole (4.75 g, 35 mmol) was added. The solution was cooled to 0° C. N-3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.69 g, 35 mmol) was added. The reaction mixture was stirred for 20 min at 0° C. A 5.6 M solution of dimethylamine in ethanol (37 ml, 209 mmol) was added. The reaction mixture was stirred for 3 days, while it was warming up to room temperature. It was diluted with ethyl acetate (400 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (400 ml). The aqueous phase was extracted with ethyl acetate (2×200 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (300 ml) and dried over magnesium sulfate. The solvent was removed in vacua. The crude product was purified by flash chromatography on silica (300 g), using dichloromethane/methanol 20:1 as eluent, to give 4.56 g of 4-(dimethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester.

1. stirringThe reaction mixture was stirred for 3 days, while it
2. temperaturewas warming up to room temperature
3. washwashed with a 10% aqueous solution of sodium hydrogen sulfate (400 ml)
4. extractionThe aqueous phase was extracted with ethyl acetate (2×200 ml)
5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (300 ml)
6. dry with materialdried over magnesium sulfate
7. customThe solvent was removed in vacua
8. customThe crude product was purified by flash chromatography on silica (300 g)

ORD record

ord-147afa6ac2454ec99e96ee59a8a26c4a

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06919315B1