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

HRID 622421Notes

Reaction equation

HRID 622421 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[CH2:58][CH2:57][N:56]([C:59](=[NH:62])[CH2:60][SH:61])[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[CH2:58][CH2:57][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])[CH2:55]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 867424292-(3-Methoxyiminopyrrolidin-1-yl)-2-iminoethylmercaptan hydrochloride

Product 1

HCID 88522642(5R,6S)-2-[2-(3-Methoxyiminopyrrolidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acidYield 5.8%

Reagents, catalysts & solvents 7

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

Procedure

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 307 mg of 2-(3-methoxyiminopyrrolidin-1-yl)-2-iminoethylmercaptan hydrochloride in 3 ml of dimethylsulfoxide was then added dropwise, and the mixture 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 2 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 23 mg of the title compound.

Workup

  1. temperaturecooling
  2. stirringthe mixture was 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-65c9328ae9944c6ba540e6a2130b0737
Source dataset
uspto-grants-1988_09
Patent number
US04771046

Reaction notes

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