Diisopropylethylamine → HCID 11025837, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence