تفاعل #1253198

معادلة التفاعل

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

المذيبات

THF

t-butanol

THF

water

THF

Methanol

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAfter 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
   أخرىThe organic phase is separated
5. 5
   استخلاصextracted into ethyl acetate (3×25 ml)
6. 6
   غسيلwashed with saline
7. 7
   تجفيفdried over magnesium sulfate
8. 8
   أخرىThe solvent is removed
9. 9
   أخرىthe residue purified by chromatography (silica
10. 10
    غسيلeluting with
11. 11
    درجة الحرارةa gradient increasing in polarity from 0 to 3% methanol in dichloromethane)

الإجراء التجريبي

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.

المصدر