反应 #8243

反应方程式

1,1′-(azodicarbonyl)dipiperidine

3-(4-Imidazol-1-yl-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one

3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole

Tributylphosphine

→

desired product

收率 158.5%

5(S)-Isoxazol-3-ylaminomethyl-3-(4-imidazol-1-yl-3-fluorophenyl)-oxazolidin-2-one

收率 158.5%

溶剂

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   过滤then filtered
2. 2
   洗涤the filter cake washed with tetrahydrofuran
3. 3
   其他The combined filtrates were evaporated
4. 4
   其他the residue purified by chromatography on a 20 g silica Mega Bond Elut® column
5. 5
   洗涤eluting with
6. 6
   温度a gradient increasing in polarity from 0 to 5% methanol in dichloromethane
7. 7
   其他evaporated
8. 8
   其他the residue triturated with diethyl ether

实验过程

3-(4-Imidazol-1-yl-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (693 mg, 2.5 mM, see WO 96-23788) and 3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole (649 mg, 2.5 mM) were suspended by stirring in dry tetrahydrofuran (25 ml) under nitrogen in an ice-bath. Tributylphosphine (808 mg, 4 mM) was added followed by 1,1′-(azodicarbonyl)dipiperidine (945 mg, 3.75 nM) dissolved in tetrahydrofuran (10 ml) over 10 minutes. The mixture was then stirred 18 hours, allowing the temperature to rise to ambient, then filtered, and the filter cake washed with tetrahydrofuran. The combined filtrates were evaporated and the residue purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined, evaporated, and the residue triturated with diethyl ether to give the desired product (1.36 g), contaminated with tributylphosphine oxide.

来源