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

HRID 622427노트

반응식

HRID 622427 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: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.[C:51]([O:54][CH:55]1[CH2:60][CH2:59][N:58]([C:61](=[NH:64])[CH2:62][SH:63])[CH2:57][CH2:56]1)(=[O:53])[NH2:52]>C(#N)C.O1CCCC1.P([O-])([O-])([O-])=O.[C].[Pd]>[C:51]([O:54][CH:55]1[CH2:60][CH2:59][N:58]([C:61](=[NH:64])[CH2:62][S:63][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][CH2:56]1)(=[O:53])[NH2:52]

참가 물질

9

반응물 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2회HCID 11198839(4-Nitrophenyl)methyl (5R,6S)-6-((1R)-1-hydroxyethyl)-3,7-dioxo-1-azabicyclo(3.2.0)heptane-2-carboxylateHCID 212929412-(4-Carbamoyloxypiperidin-1-yl)-2-iminoethylmercaptan hydrochloride

생성물 1

HCID 22839818(5R,6S)-2-[2-(4-Carbamoyloxypiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid수율 19%

시약·촉매·용매 4

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

실험 절차

1.83 ml of diisopropylethylamine and 2.18 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 3.48 g of 4-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 20 ml of anhydrous acetonitrile, and the mixture was stirred for one hour with ice-cooling. The reaction mixture was then added to a mixture of 2.1 ml of diisopropylethylamine in 70 ml of tetrahydrofuran and 60 ml of 0.1M phosphate buffer solution (pH 7.0), which had been cooled with ice and salt, together with 10 ml of an aqueous solution of 3.17 g of 2-(4-carbamoyloxypiperidin-1-yl)-2-iminoethylmercaptan hydrochloride, and the resulting mixture was stirred for 5 minutes. The reaction mixture was then subjected to hydrogenation at room temperature for 2 hours, in the presence of 3.0 g of 10% palladium-carbon. The hydrogenated reaction mixture was worked up in the same manner as in Example 1(3), giving 783 mg of the title compound.

후처리

  1. temperaturecooling
  2. stirringthe resulting mixture was stirred for 5 minutes

출처 및 근거

ORD 기록
ord-b8bc481851a240898d8564c3274404a1
출처 데이터셋
uspto-grants-1988_09
특허 번호
US04771046

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