Réaction #8243

Équation de réaction

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

Rendement 158.5%

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

Rendement 158.5%

Solvants

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Filtrationthen filtered
2. 2
   Lavagethe filter cake washed with tetrahydrofuran
3. 3
   AutreThe combined filtrates were evaporated
4. 4
   Autrethe residue purified by chromatography on a 20 g silica Mega Bond Elut® column
5. 5
   Lavageeluting with
6. 6
   Températurea gradient increasing in polarity from 0 to 5% methanol in dichloromethane
7. 7
   Autreevaporated
8. 8
   Autrethe residue triturated with diethyl ether

Mode opératoire

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.

Source