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

HRID 622432노트

반응식

HRID 622432 반응식
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:38](=[O:39])[N:30]2[CH:31]([C:35]([O-:37])=[O:36])[C:32](=O)[CH2:33][C@H:29]12)[CH3:27].Cl.[O:41]=[C:42]1[NH:47][CH2:46][CH2:45][N:44]([C:48](=[NH:51])[CH2:49][SH:50])[CH2:43]1>C(#N)C.O1CCCC1.P([O-])([O-])([O-])=O.[C].[Pd]>[O:41]=[C:42]1[NH:47][CH2:46][CH2:45][N:44]([C:48](=[NH:51])[CH2:49][S:50][C:32]2[CH2:33][C@@H:29]3[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:38](=[O:39])[N:30]3[C:31]=2[C:35]([OH:37])=[O:36])[CH2:43]1

참가 물질

9

반응물 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2회HCID 18600095(5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylateHCID 212929952-(3-Oxopiperazin-1-yl)-2-iminoethylmercaptan hydrochloride

생성물 1

HCID 22839798(5R,6S)-2-[2-(3-Oxopiperazin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid수율 17.3%

시약·촉매·용매 4

HCID 178418390HCID 178418390, 화합물촉매HCID 1061Phosphate용매HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매

실험 절차

1.62 ml of diisopropylethylamine and 1.92 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 3.0 g of (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 36 ml of anhydrous acetonitrile, and the mixture was stirred for one hour with ice-cooling. The reaction mixture was then added to an ice-cooled mixture of 1.86 ml of diisopropylethylamine in 180 ml of tetrahydrofuran and 160 ml of 0.1M phosphate buffer solution (pH 7.0), together with 20 ml of an aqueous solution of 2.79 g of 2-(3-oxopiperazin-1-yl)-2-iminoethylmercaptan hydrochloride, and the resulting mixture was stirred for 50 minutes. The reaction mixture was then subjected to hydrogenation at room temperature for 2.5 hours, in the presence of 3.0 g of 10% palladium-carbon. The hydrogenated mixture was filtered over "Celite" (Trade Mark) filter aid, and the filtrate was extracted with 200 ml of ether. The aqueous layer was concentrated under reduced pressure, and the concentrate was subjected to chromatography through a 250 ml column of "Dowex 50W" (Trade Mark) cation exchange resin (Na+ type), giving 850 mg of the title product from the fraction eluted with water.

후처리

  1. temperaturecooling
  2. temperaturecooled
  3. filtrationThe hydrogenated mixture was filtered over "Celite" (Trade Mark)
  4. filtrationfilter aid
  5. extractionthe filtrate was extracted with 200 ml of ether
  6. concentrationThe aqueous layer was concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-10617a8c74344b139b29c83a4f54f419
출처 데이터셋
uspto-grants-1988_09
특허 번호
US04771046

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