Diisopropylethylamine → tert-Butyl methylcarbamate

At 0° C., N-3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (416 mg, 2.17 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)-propioni acid (715 mg, 2.17 mmol) and 1-hydroxy-7-azabenzotriazole (296 mg, 2.17 mmol) in dichloromethane (20 ml) and N,N-dimethyformamide (10 ml). The reaction mixture was stirred for 20 min at 0° c. A solution of (2R)-1-(4-((dimethylamino)methyl)piperidin-1-yl)-2-(methylamino)-3-phenylpropan-1-one (659 mg, 2.17 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (5 ml) and ethyldiisopropylamine (0.56 ml, 3.26 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (100 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml). The aqueous solution was extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography 60 on silica (80 g), using ethyl acetate/heptane/triethylamine (1:1:0.08) as eluent, to give 1.05 g of N-((1R)-1-{N-[(1R)-1-benzyl-2-(4-(dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

1. stirringThe reaction mixture was stirred for 16 h, while it
2. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml)
3. extractionThe aqueous solution was extracted with ethyl acetate (3×50 ml)
4. dry with materialThe combined organic layers were dried over magnesium sulfate
5. customThe solvent was removed in vacuo
6. customThe crude product was purified by flash chromatography 60 on silica (80 g)

ORD record

ord-305fdf7db7be40728283b8f0f8a9f48f

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06919315B1