Diphenylphosphinic chloride → (5R,6S)-2-[2-(4-Hydroxyiminopiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid

HRID 622415ノート

反応式

HRID 622415 の反応式
C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[OH:25][C@@H:26]([C@H:28]1[C:48](=[O:49])[N:30]2[CH:31]([C:35]([O:37]CC3C=CC([N+]([O-])=O)=CC=3)=[O:36])[C:32](=O)[CH2:33][C@H:29]12)[CH3:27].Cl.[OH:51][N:52]=[C:53]1[CH2:58][CH2:57][N:56]([C:59](=[NH:62])[CH2:60][SH:61])[CH2:55][CH2:54]1>C(#N)C.CS(C)=O.O1CCCC1.O.P([O-])([O-])([O-])=O.[C].[Pd].CCOCC>[OH:51][N:52]=[C:53]1[CH2:54][CH2:55][N:56]([C:59](=[NH:62])[CH2:60][S:61][C:32]2[CH2:33][C@@H:29]3[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:48](=[O:49])[N:30]3[C:31]=2[C:35]([OH:37])=[O:36])[CH2:57][CH2:58]1

参加物

12

反応物 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2 回HCID 11198839(4-Nitrophenyl)methyl (5R,6S)-6-((1R)-1-hydroxyethyl)-3,7-dioxo-1-azabicyclo(3.2.0)heptane-2-carboxylateHCID 212929702-(4-Hydroxyiminopiperidin-1-yl)-2-iminoethylmercaptan hydrochloride

生成物 1

HCID 22839800(5R,6S)-2-[2-(4-Hydroxyiminopiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid収率 6.8%

試薬・触媒・溶媒 7

HCID 178418390HCID 178418390、化合物触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 1061Phosphate溶媒HCID 3283Diethyl Ether溶媒HCID 6342Acetonitrile溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

0.21 ml of diisopropylethylamine and 0.22 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 363 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 one hour with ice-cooling. A solution of 0.18 ml of diisopropylethylamine and 324 mg of 2-(4-hydroxyiminopiperidin-1-yl)-2-iminoethylmercaptan hydrochloride in 3 ml of dimethylsulfoxide was then added dropwise to the mixture, which was stirred for a further 20 minutes with ice-cooling. The reaction mixture was then poured into 100 ml of anhydrous ether, and the solvent was decanted off from the gummy material which formed. This material was dissolved in a mixture of 20 ml of tetrahydrofuran, 7 ml of water and 23 ml of 0.1M phosphate buffer (pH 7.0), and the solution was subjected to catalytic hydrogenation at room temperature for 4 hours in the presence of 0.3 g of 10% palladium-carbon. The hydrogenated solution was filtered over "Celite" (Trade Mark) filter aid, the filtrate was extracted with 200 ml of ether, and the aqueous layer was concentrated under reduced pressure. The concentrate was subjected to chromatography using a 300 ml column of "Dowex 50W" (Trade Mark) cation exchange resin (Na+ type), and 27 mg of the title compound were obtained from the fraction eluted with water.

後処理

  1. temperaturecooling
  2. stirringwas stirred for a further 20 minutes with ice-
  3. temperaturecooling
  4. customthe solvent was decanted off from the gummy material which
  5. customformed
  6. filtrationThe hydrogenated solution was filtered over "Celite" (Trade Mark)
  7. filtrationfilter aid
  8. extractionthe filtrate was extracted with 200 ml of ether
  9. concentrationthe aqueous layer was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-9eb9df5df6a24e0bb3454a2639d46ffa
出典データセット
uspto-grants-1988_09
特許番号
US04771046

反応ノート

読み込み中…