تفاعل #8245

معادلة التفاعل

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

المردود 13.9%

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

المردود 13.9%

المذيبات

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwere added
2. 2
   ترشيحthen filtered
3. 3
   غسيلthe filter cake washed with tetrahydrofuran
4. 4
   أخرىThe combined filtrates were evaporated
5. 5
   أخرىthe residue purified by chromatography on a 10 g
6. 6
   غسيلeluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% trifluoroacetic acid
7. 7
   أخرىevaporated
8. 8
   أخرىthe residue rechromatographed on a 10 g silica Mega Bond Elut® column
9. 9
   غسيلeluting with
10. 10
    درجة الحرارةa gradient increasing in polarity from 0 to 20% methanol in dichloromethane
11. 11
    أخرىevaporated

الإجراء التجريبي

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

المصدر