反応 #8243

反応方程式

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

収率 158.5%

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

収率 158.5%

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   ろ過then filtered
2. 2
   洗浄the filter cake washed with tetrahydrofuran
3. 3
   その他The combined filtrates were evaporated
4. 4
   その他the residue purified by chromatography on a 20 g silica Mega Bond Elut® column
5. 5
   洗浄eluting with
6. 6
   温度a gradient increasing in polarity from 0 to 5% methanol in dichloromethane
7. 7
   その他evaporated
8. 8
   その他the residue triturated with diethyl ether

実験手順

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.

出典