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

HRID 622434
Notes
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Reaction equation

HRID 622434 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:49](=[O:50])[N:30]2[CH:31]([C:36]([O:38]CC3C=CC([N+]([O-])=O)=CC=3)=[O:37])[C:32](=O)[C@H:33]([CH3:34])[C@H:29]12)[CH3:27].Cl.[C:52]([O:55][C@@H:56]1[CH2:60][CH2:59][N:58]([C:61](=[NH:64])[CH2:62][SH:63])[CH2:57]1)(=[O:54])[NH2:53]>C(#N)C.CS(C)=O.O1CCCC1.P([O-])([O-])([O-])=O.[C].[Pd].CCOCC>[C:52]([O:55][C@@H:56]1[CH2:60][CH2:59][N:58]([C:61](=[NH:64])[CH2:62][S:63][C:32]2[C@H:33]([CH3:34])[C@@H:29]3[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:49](=[O:50])[N:30]3[C:31]=2[C:36]([OH:38])=[O:37])[CH2:57]1)(=[O:54])[NH2:53]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

11

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×HCID 98853021-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)-HCID 867424262-[(3R)-3-carbamoyloxypyrrolidin-1-yl]-2-iminoethylmercaptan hydrochloride

Product 1

HCID 22839794
(1R,5S,6S)-2-{2-[(3R)-3-Carbamoyloxypyrrolidin-1-yl]-2-iminoethylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid
Yield 23.2%

Reagents, catalysts & solvents 6

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

Procedure

0.28 ml of diisopropylethylamine and 0.29 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 500 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 6 ml of anhydrous acetonitrile, and then the mixture was stirred for one hour with ice-cooling. 0.20 ml of diisopropylethylamine and a solution of 458 mg of 2-[(3R)-3-carbamoyloxypyrrolidin-1-yl]-2-iminoethylmercaptan hydrochloride in 3.6 ml of dimethylsulfoxide were added to the reaction mixture, and then the whole mixture was stirred for a further 30 minutes with ice-cooling. The reaction mixture was poured into 200 ml of anhydrous ether and the solvent was decanted off from the gummy material which formed. This material was dissolved in a mixture of 40 ml of tetrahydrofuran and 46 ml of 0.1M phosphate buffer (pH 7.0), and the solution was subjected to hydrogenation for 2 hours at room temperature in the presence of 0.6 g of 10% palladium-carbon. The hydrogenation mixture was filtered over "Celite" (Trade Mark) filter aid, and the filtrate was extracted with 80 ml of ether. The aqueous layer was concentrated under reduced pressure and the concentrate was subjected to chromatography through a 160 ml column of "Dowex 50W" (Trade Mark) cation exchange resin (Na+ type), giving 132 mg of the title product from the fraction eluted with water.

Workup

  1. temperaturecooling
  2. stirringthe whole mixture was stirred for a further 30 minutes with ice-
  3. temperaturecooling
  4. customthe solvent was decanted off from the gummy material which
  5. customformed
  6. filtrationThe hydrogenation mixture was filtered over "Celite" (Trade Mark)
  7. filtrationfilter aid
  8. extractionthe filtrate was extracted with 80 ml of ether
  9. concentrationThe aqueous layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ca7849b388f048959ccd4b45e57c01af
Source dataset
uspto-grants-1988_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04771046

Reaction notes

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