Reacción #1987372

Ecuación de reacción

isobutyl chloroformate

N-methylpiperidine

(-)-2-(4-cyanophenoxy)-1-methylethylamine

N-(4-fluorophenoxycarbonyl)-L-valine

→

desired product

Rendimiento 22.6%

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

Rendimiento 22.6%

Disolventes

methylene chloride

Water

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added to the mixture
2. 2
   Temperaturawarm naturally to room temperature
3. 3
   workup.STIRRINGwhile being stirred
4. 4
   workup.STIRRINGwas stirred 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
   OtroThe obtained crude crystal
9. 9
   Otrowas purified by column chromatography on silica gel

Procedimiento

1.2 g of N-methylpiperidine was added to a solution containing 3.0 g of N-(4-fluorophenoxycarbonyl)-L-valine dissolved in 80 ml of methylene chloride, at -20° C. After the mixture was stirred for 15 minutes at the same temperature, 1.6 g of isobutyl chloroformate was added to the mixture, and stirred for 1 hour at -20° C. 2.3 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, and 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 obtained 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 crystal (yield: 23% ).

Fuente