반응 #1253198

반응 방정식

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

용매

THF

t-butanol

THF

water

THF

Methanol

반응 조건

후처리

1. 1
   온도After 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
   기타The organic phase is separated
5. 5
   추출extracted into ethyl acetate (3×25 ml)
6. 6
   세척washed with saline
7. 7
   건조dried over magnesium sulfate
8. 8
   기타The solvent is removed
9. 9
   기타the residue purified by chromatography (silica
10. 10
    세척eluting with
11. 11
    온도a gradient increasing in polarity from 0 to 3% methanol in dichloromethane)

실험 절차

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.

출처