反応 #709594

ord-f454963437c146f187095cf0c53c0dea

反応方程式

C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)C[C@H]12
p-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate
CCN(C(C)C)C(C)C
diisopropylethylamine
Cl.N=C(CS)N1CC[C@@H](OC(N)=O)C1
2-[(3R)-3-carbamoyloxypyrrolidin-1-yl]-2-iminoethylmercaptan hydrochloride
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)O)=C(SCC(=N)N3CC[C@@H](OC(N)=O)C3)C[C@H]12
title product
収率 17.6%
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(SCC(=N)N3CC[C@@H](OC(N)=O)C3)C[C@H]12
(5R,6S)-2-{2-[(3R)-3-Carbamoyloxypyrrolidin-1-yl]-2-iminoethylthio}-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid
収率 17.6%

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度cooling
  2. 2
    workup.STIRRINGthe resulting mixture was stirred for a further 30 minutes with ice-
  3. 3
    温度cooling
  4. 4
    その他the solvent was decanted off from the gummy material which
  5. 5
    その他formed
  6. 6
    ろ過The hydrogenated solution was filtered over "Celite" (Trade Mark)
  7. 7
    ろ過filter aid
  8. 8
    抽出the filtrate was extracted with 80 ml of ether
  9. 9
    濃縮The aqueous layer was concentrated under reduced pressure

実験手順

0.183 ml of diisopropylethylamine and 0.218 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 348 mg of p-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 5 ml of anhydrous acetonitrile, and the mixture was stirred for 60 minutes with ice-cooling. A solution of 0.183 ml of diisopropylethylamine and 380 mg of 2-[(3R)-3-carbamoyloxypyrrolidin-1-yl]-2-iminoethylmercaptan hydrochloride in 2.5 ml of dimethylsulfoxide was then added dropwise, and the resulting mixture was stirred for a further 30 minutes with ice-cooling. The reaction mixture was poured into 200 ml of anhydrous ether, and the solvent was decanted off from the gummy material which formed. This material was dissolved in a mixture of 35 ml of tetrahydrofuran and 35 ml of 0.1M phosphate buffer (pH 7.0), and the solution was subjected to catalytic hydrogenation for 3 hours at room temperature in the presence of 0.55 g of 10% palladium-carbon. The hydrogenated solution was filtered over "Celite" (Trade Mark) filter aid, and the filtrate was extracted with 80 ml of ether. The aqueous layer was concentrated under reduced pressure, and the concentrate was subjected to chromatography through a 160 ml of column of "Dowex 50W" (Trade Mark) cation exchange resin (Na+ type), giving 70 mg of the title product from the fraction eluted with water.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US04771046uspto-grants-1988_09