Reacción #1253198

Ecuación de reacción

n-butyllithium

(R)-glycidylbutyrate

5-benzyloxycarbonylamino-2-(4-[2 fluoroethyl]-3-oxopiperazin-1-yl)fluorobenzene

sodium bicarbonate

→

lithium t-butoxide

(5R)-3-(3-fluoro-4-[4-(2-fluoroethyl)-3-oxopiperazin-1-yl]phenyl)-5 hydroxymethyloxazolidin-2-one

Disolventes

THF

t-butanol

THF

water

THF

Methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling to −70°
2. 2
   workup.WAITcontinued at −70° for 15 minutes
3. 3
   workup.WAITto rise to 20-25° over 16 hours
4. 4
   OtroThe organic phase is separated
5. 5
   Extracciónextracted into ethyl acetate (3×25 ml)
6. 6
   Lavadowashed with saline
7. 7
   Secadodried over magnesium sulfate
8. 8
   OtroThe solvent is removed
9. 9
   Otrothe residue purified by chromatography (silica
10. 10
    Lavadoeluting with
11. 11
    Temperaturaa gradient increasing in polarity from 0 to 3% methanol in dichloromethane)

Procedimiento

A solution of lithium t-butoxide is prepared by addition of n-butyllithium (1.6 M in hexane, 2.9 ml) to a stirred solution of t-butanol (0.43 g) in anhydrous THF (10 ml) at −10° under argon. After cooling to −70°, a solution of 5-benzyloxycarbonylamino-2-(4-[2 fluoroethyl]-3-oxopiperazin-1-yl)fluorobenzene (1.5 g) in dry THF (15 ml) is added. After 10 minutes, (R)-glycidylbutyrate (0.67 g) in dry THF (15 ml) is added to the resulting mixture, and stirring continued at −70° for 15 minutes, before allowing the temperature to rise to 20-25° over 16 hours. Methanol (10 ml) is added, followed by saturated sodium bicarbonate solution (20 ml) and water (10 ml). The organic phase is separated and extracted into ethyl acetate (3×25 ml), washed with saline and dried over magnesium sulfate. The solvent is removed and the residue purified by chromatography (silica; eluting with a gradient increasing in polarity from 0 to 3% methanol in dichloromethane) to give (5R)-3-(3-fluoro-4-[4-(2-fluoroethyl)-3-oxopiperazin-1-yl]phenyl)-5 hydroxymethyloxazolidin-2-one.

Fuente