Diisopropylethylamine → HCID 11025837、化合物

温度

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レコード

ord-725f8c8cc59842cda779ecf3865fadaf

出典データセット

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07576062B2