Reaktion #1253198

Reaktionsgleichung

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

Lösungsmittel

THF

t-butanol

THF

water

THF

Methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter 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
   SonstigeThe organic phase is separated
5. 5
   Extraktionextracted into ethyl acetate (3×25 ml)
6. 6
   Waschenwashed with saline
7. 7
   Trocknendried over magnesium sulfate
8. 8
   SonstigeThe solvent is removed
9. 9
   Sonstigethe residue purified by chromatography (silica
10. 10
    Wascheneluting with
11. 11
    Temperatura gradient increasing in polarity from 0 to 3% methanol in dichloromethane)

Vorschrift

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.

Quelle