N-Methylpiperidine → N1-[2-(4-cyanophenoxy)-1-methylethyl]-N2-phenoxycarbonyl-L-valinamide

Temperature

-20 °C

0.6 g of N-methylpiperidine was added to a solution containing 1.5 g of N-(4-methylbenzyloxycarbonyl)-L-valine dissolved in 100 ml of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature, 0.8 g of isobutyl chloroformate was added to the mixture, and subsequently the whole mixture was stirred for 1 hour at -20° C. 1.0 g of 2-(4-cyanophenoxy)-1-methylethylamine was added to this mixture at -60° C., and then the reaction mixture was allowed to sit and warm naturally to room temperature while being stirred. The whole mixture was stirred for 20 hours at room temperature. Water was subsequently added to the reaction mixture. After the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water, the organic layer was dried over anhydrous magnesium sulfate and the methylene chloride was removed under reduced pressure. The residue, which was a crude crystal, was purified by column chromatography on silica gel, thus yielding 0.6 g of the desired product in the form of light white powder (yield: 28%).

1. additionwas added to the mixture
2. temperaturewarm naturally to room temperature
3. stirringwhile being stirred
4. stirringThe whole mixture was stirred for 20 hours at room temperature
5. washAfter the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water
6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
7. customthe methylene chloride was removed under reduced pressure
8. customwas purified by column chromatography on silica gel

ORD record

ord-0846c5047ba94a3b89f2b489d123d67c

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05811424