反応 #8245

反応方程式

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

収率 13.9%

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

収率 13.9%

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   workup.ADDITIONwere added
2. 2
   ろ過then filtered
3. 3
   洗浄the filter cake washed with tetrahydrofuran
4. 4
   その他The combined filtrates were evaporated
5. 5
   その他the residue purified by chromatography on a 10 g
6. 6
   洗浄eluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% trifluoroacetic acid
7. 7
   その他evaporated
8. 8
   その他the residue rechromatographed on a 10 g silica Mega Bond Elut® column
9. 9
   洗浄eluting with
10. 10
    温度a gradient increasing in polarity from 0 to 20% methanol in dichloromethane
11. 11
    その他evaporated

実験手順

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

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