تفاعل #449275

معادلة التفاعل

diphenylphosphoryl chloride

diisopropylethylamine

4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate

diisoproylethylamine

(2S,4S)-4-mercapto-2-[(3S)-3-(1-1,2,4-triazolyl)-1-pyrrolidinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

→

title compound

المردود 70.1%

4-Nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(2S,4S)-1-(4-nitrobenzyloxycarbonyl)-2-[(3S)-3-(1-1,2,4-triazolyl)-1-pyrrolidinylcarbonyl]pyrrolidin-4-ylthio]-1-carbapen-2-em-3-carboxylate

المردود 70.1%

المذيبات

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooling, to the resulting solution
2. 2
   درجة الحرارةcooling, to the resulting mixture
3. 3
   workup.STIRRINGthe mixture was stirred at the same temperature for 6 hours
4. 4
   أخرىThe solvent was then removed by distillation under reduced pressure
5. 5
   workup.DISSOLUTIONthe resulting residue was dissolved in ethyl acetate
6. 6
   غسيلThe resulting solution was then washed with water, with an aqueous solution of sodium hydrogencarbonate, again with water and finally with a saturated aqueous solution of sodium chloride
7. 7
   استخلاصThe aqueous layer was extracted with methylene chloride
8. 8
   تجفيفdried over anhydrous magnesium sulfate
9. 9
   أخرىThe solvent was removed by distillation under reduced pressure
10. 10
    أخرىthe residue was purified by silica gel column chromatography
11. 11
    workup.ADDITIONby volume mixture of ethyl acetate and methanol as the eluent

الإجراء التجريبي

486 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate were dissolved in 5 ml of dry acetonitrile, and 379 mg of diphenylphosphoryl chloride and 182 mg of diisopropylethylamine were added dropwise, with ice-cooling, to the resulting solution. The mixture was then stirred at the same temperature for 1 hour. At the end of this time, a solution of 173 mg of diisoproylethylamine and 690 mg of (2S,4S)-4-mercapto-2-[(3S)-3-(1-1,2,4-triazolyl)-1-pyrrolidinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 119) in 4 ml of dry acetonitrile was added dropwise with ice-cooling, to the resulting mixture, and the mixture was stirred at the same temperature for 6 hours. The solvent was then removed by distillation under reduced pressure, and the resulting residue was dissolved in ethyl acetate. The resulting solution was then washed with water, with an aqueous solution of sodium hydrogencarbonate, again with water and finally with a saturated aqueous solution of sodium chloride. The aqueous layer was extracted with methylene chloride, and the aqueous layer was combined with the washings and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography, using a 5:1 by volume mixture of ethyl acetate and methanol as the eluent, to obtain 744 mg of the title compound, as a powder.

المصدر