تفاعل #552523

ord-e441ced7f4a44e6ab3dcd006190ae695

معادلة التفاعل

CCN(C(C)C)C(C)C
diisopropylethylamine
O=P(Cl)(c1ccccc1)c1ccccc1
diphenylphosphoryl chloride
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2-oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester
S=C1NCC[C@H]1S
(3R)-3-mercaptopyrrolidine-2-thione
CCN(C(C)C)C(C)C
diisopropylethylamine
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CCNC3=S)[C@H](C)[C@H]12
(1R, 5S, 6S)-2-[(3R)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester
المردود 39.3%

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.STIRRINGThe mixture is stirred at the same temperature for 1.5 hour
  2. 2
    تركيزThe mixture is concentrated under reduced pressure
  3. 3
    أخرىto remove acetonitrile
  4. 4
    استخلاصThe residue is extracted with ethyl acetate
  5. 5
    غسيلthe extract is washed with water
  6. 6
    أخرىdried
  7. 7
    أخرىevaporated to dryness under reduced pressure
  8. 8
    أخرىThe residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1)

الإجراء التجريبي

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2-oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester (8.3 g) is dissolved in anhydrous acetonitrile (50 ml), and thereto are added dropwise diisopropylethylamine (4 ml) and diphenylphosphoryl chloride (4.8 ml) in this order under nitrogen gas below 0° C. After stirring the mixture at the same temperature for 30 minutes, a solution of (3R)-3-mercaptopyrrolidine-2-thione (4 g) and diisopropylethylamine (4 ml) in anhydrous acetonitrile (50 ml) is added dropwise to the reaction mixture below -15° C. The mixture is stirred at the same temperature for 1.5 hour, and water (50 ml) is added to the reaction mixture. The mixture is concentrated under reduced pressure to remove acetonitrile. The residue is extracted with ethyl acetate, and the extract is washed with water, dried and evaporated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1) to give (1R, 5S, 6S)-2-[(3R)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester (4.3 g) as an amorphous powder.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US05153187uspto-grants-1992_10