Diisopropylethylamine → HCID 11025837, Verbindung

Temperatur

0 °C

At 0° C. N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (870 mg, 4.54 mmol) was added to a solution (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-phenylpropionic acid (1.27 g, 4.54 mmol) and 1-hydroxy-7-azabenzotriazole (617 mg, 4.54 mmol) in dichloromethane (20 ml) and N,N-dimethylformamide (10 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of the crude dihydrochloride salt of N,N-dimethyl-N-(((3R)-piperidin-3-yl)methyl)amine (976 mg, 4.54 mmol) in dichloromethane (20 ml) and N,N-dimethylformamide (10 ml) and ethyldiisopropylamine (3.9 ml, 22.7 mmol) were added successively. The reaction mixture was stirred for 3 days, while it was warming up to room temperature. Ethyl acetate (300 ml) was added. The solution was washed with a saturated aqueous solution of sodium hydrogen carbonate (300 ml). The aqueous phase was extracted with ethyl acetate (2×200 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 1.69 g of N-[(1R)-1-benzyl-2-((3S)-3-(dimethylaminomethyl)piperidin-1-yl)-2-oxoethyl]-N-methylcarbamic acid tert-butyl ester.

1. customAt 0° C
2. stirringThe reaction mixture was stirred for 3 days, while it
3. temperaturewas warming up to room temperature
4. washThe solution was washed with a saturated aqueous solution of sodium hydrogen carbonate (300 ml)
5. extractionThe aqueous phase was extracted with ethyl acetate (2×200 ml)
6. dry with materialThe combined organic layers were dried over magnesium sulfate
7. customThe solvent was removed in vacuo
8. customThe crude product was purified by flash chromatography on silica (90 g)

ORD-Eintrag

ord-0d3fa30dc138491586932ba87eda8ce0

Quelldatensatz

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06919315B1