반응 #8243

반응 방정식

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

수율 158.5%

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

수율 158.5%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   여과then filtered
2. 2
   세척the filter cake washed with tetrahydrofuran
3. 3
   기타The combined filtrates were evaporated
4. 4
   기타the residue purified by chromatography on a 20 g silica Mega Bond Elut® column
5. 5
   세척eluting with
6. 6
   온도a gradient increasing in polarity from 0 to 5% methanol in dichloromethane
7. 7
   기타evaporated
8. 8
   기타the residue triturated with diethyl ether

실험 절차

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.

출처