反应 #8245

反应方程式

1,1′-(azo-dicarbonyl)dipiperidine

3-(4-(4-t-Butyldimethylsilyloxymethylimidazol-1-yl)-3-fluorophenyl)-5(R)-hydroxy-methyloxazolidin-2-one

3-(t-butoxycarbonyl-amino)isoxazole

Tributylphosphine

→

desired product

收率 13.9%

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

收率 13.9%

溶剂

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   workup.ADDITIONwere added
2. 2
   过滤then filtered
3. 3
   洗涤the filter cake washed with tetrahydrofuran
4. 4
   其他The combined filtrates were evaporated
5. 5
   其他the residue purified by chromatography on a 10 g
6. 6
   洗涤eluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% trifluoroacetic acid
7. 7
   其他evaporated
8. 8
   其他the residue rechromatographed on a 10 g silica Mega Bond Elut® column
9. 9
   洗涤eluting with
10. 10
    温度a gradient increasing in polarity from 0 to 20% methanol in dichloromethane
11. 11
    其他evaporated

实验过程

3-(4-(4-t-Butyldimethylsilyloxymethylimidazol-1-yl)-3-fluorophenyl)-5(R)-hydroxy-methyloxazolidin-2-one (842 mg, 2 mM, see WO 97-31917) and 3-(t-butoxycarbonyl-amino)isoxazole (405 mg, 2.2 mM) were suspended by stirring in dry tetrahydrofuran (15 ml) under nitrogen in an ice-bath. Tributylphosphine (444 mg, 2.2 mM) followed by 1,1′-(azo-dicarbonyl)dipiperidine (555 mg, 2.2 mM) dissolved in tetrahydrofuran (10 ml) were added. 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 10 g reversed phase C18 column, eluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% trifluoroacetic acid. Relevant fractions were combined, evaporated, and the residue rechromatographed on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 20% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (104 mg). MS (ESP): 474 (MH+) for C22H24FN5O6

来源