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

HRID 622418Notes

Reaction equation

HRID 622418 reaction equation
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.[CH3:51][O:52][N:53]=[C:54]1[CH2:59][CH2:58][N:57]([C:60](=[NH:63])[CH2:61][SH:62])[CH2:56][CH2:55]1>C(#N)C.CS(C)=O.O1CCCC1.O.P([O-])([O-])([O-])=O.[C].[Pd].CCOCC>[CH3:51][O:52][N:53]=[C:54]1[CH2:59][CH2:58][N:57]([C:60](=[NH:63])[CH2:61][S:62][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])[CH2:56][CH2:55]1

Participants

12

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×HCID 11198839(4-Nitrophenyl)methyl (5R,6S)-6-((1R)-1-hydroxyethyl)-3,7-dioxo-1-azabicyclo(3.2.0)heptane-2-carboxylateHCID 212930122-(4-Methoxyiminopiperidin-1-yl)-2-iminoethylmercaptan hydrochloride

Product 1

HCID 22839819(5R,6S)-2-[2-(4-Methoxyiminopiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acidYield 4.4%

Reagents, catalysts & solvents 7

HCID 178418390HCID 178418390, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 1061PhosphateSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

0.22 ml of diisopropylethylamine and 0.21 ml of diphenylphosphoryl chloride was 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 394 mg of 2-(4-methoxyiminopiperidin-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 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 3 hours in the presence of 0.3 g of 10% palladium-carbon. The product was worked up and purified in the same manner as in Example 2, giving 18 mg of the title compound.

Workup

  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. custompurified in the same manner as in Example 2

Sources & evidence

ORD record
ord-f88cdace1acc43438e6089f997cbf411
Source dataset
uspto-grants-1988_09
Patent number
US04771046

Reaction notes

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