Réaction #8245

Équation de réaction

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

Rendement 13.9%

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

Rendement 13.9%

Solvants

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

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

Mode opératoire

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

Source