반응 #8245

반응 방정식

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

수율 13.9%

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

수율 13.9%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.ADDITIONwere added
2. 2
   여과then filtered
3. 3
   세척the filter cake washed with tetrahydrofuran
4. 4
   기타The combined filtrates were evaporated
5. 5
   기타the residue purified by chromatography on a 10 g
6. 6
   세척eluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% trifluoroacetic acid
7. 7
   기타evaporated
8. 8
   기타the residue rechromatographed on a 10 g silica Mega Bond Elut® column
9. 9
   세척eluting with
10. 10
    온도a gradient increasing in polarity from 0 to 20% methanol in dichloromethane
11. 11
    기타evaporated

실험 절차

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

출처