反応 #1253198

反応方程式

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

溶媒

THF

t-butanol

THF

water

THF

Methanol

反応条件

後処理

1. 1
   温度After 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
   その他The organic phase is separated
5. 5
   抽出extracted into ethyl acetate (3×25 ml)
6. 6
   洗浄washed with saline
7. 7
   乾燥dried over magnesium sulfate
8. 8
   その他The solvent is removed
9. 9
   その他the residue purified by chromatography (silica
10. 10
    洗浄eluting with
11. 11
    温度a gradient increasing in polarity from 0 to 3% methanol in dichloromethane)

実験手順

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.

出典