Reacción #1987354

Ecuación de reacción

isobutyl chloroformate

N-methylpiperidine

2-(4-cyanophenoxy)-1-methylethylamine

N-phenoxycarbonyl-L-valine

→

desired product

Rendimiento 22.3%

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

Rendimiento 22.3%

Disolventes

methylene chloride

Water

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added to the mixture at -40° C.
2. 2
   Temperaturawarm naturally to room temperature
3. 3
   workup.STIRRINGwith stirring
4. 4
   workup.STIRRINGstirred for 20 hours at room temperature
5. 5
   LavadoAfter the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water
6. 6
   Secadothe organic layer was dried over anhydrous magnesium sulfate
7. 7
   Otrothe methylene chloride was removed under reduced pressure
8. 8
   Otrowas purified by column chromatography on silica gel

Procedimiento

1.3 g of N-methylpiperidine was added to a solution containing 3 g of N-phenoxycarbonyl-L-valine dissolved in 50 mL of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature, 1.7 g of isobutyl chloroformate was added to the mixture at -40° C., and stirred for 1 hour at -20° C. 2.2 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, with stirring, and 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 obtaining 1.1 g of the desired product in the form of a white powder (yield: 22%).

Fuente