Diphenylphosphinic chloride → HCID 131717559, compound

HRID 465341Notes

Reaction equation

HRID 465341 reaction equation
[N+:1]([C:4]1[CH:26]=[CH:25][C:7]([CH2:8][O:9][C:10]([CH:12]2[N:16]3[C:17](=[O:22])[C@H:18]([C@H:19]([OH:21])[CH3:20])[C@H:15]3[C@@H:14]([CH3:23])[C:13]2=O)=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[SH:51][C@@H:52]1[CH2:56][CH2:55][NH:54][C:53]1=[S:57]>C(#N)C.O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][C:10]([C:12]2[N:16]3[C:17](=[O:22])[C@H:18]([C@H:19]([OH:21])[CH3:20])[C@H:15]3[C@@H:14]([CH3:23])[C:13]=2[S:51][C@@H:52]2[CH2:56][CH2:55][NH:54][C:53]2=[S:57])=[O:11])=[CH:25][CH:26]=1)([O-:3])=[O:2]

Participants

7

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 54175447HCID 54175447, compound

Product 1

HCID 131717559HCID 131717559, compoundYield 39.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2-oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester (8.3 g) is dissolved in anhydrous acetonitrile (50 ml), and thereto are added dropwise diisopropylethylamine (4 ml) and diphenylphosphoryl chloride (4.8 ml) in this order under nitrogen gas below 0° C. After stirring the mixture at the same temperature for 30 minutes, a solution of (3R)-3-mercaptopyrrolidine-2-thione (4 g) and diisopropylethylamine (4 ml) in anhydrous acetonitrile (50 ml) is added dropwise to the reaction mixture below -15° C. The mixture is stirred at the same temperature for 1.5 hour, and water (50 ml) is added to the reaction mixture. The mixture is concentrated under reduced pressure to remove acetonitrile. The residue is extracted with ethyl acetate, and the extract is washed with water, dried and evaporated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1) to give (1R, 5S, 6S)-2-[(3R)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester (4.3 g) as an amorphous powder.

Workup

  1. stirringThe mixture is stirred at the same temperature for 1.5 hour
  2. concentrationThe mixture is concentrated under reduced pressure
  3. customto remove acetonitrile
  4. extractionThe residue is extracted with ethyl acetate
  5. washthe extract is washed with water
  6. customdried
  7. customevaporated to dryness under reduced pressure
  8. customThe residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1)

Sources & evidence

ORD record
ord-e441ced7f4a44e6ab3dcd006190ae695
Source dataset
uspto-grants-1992_10
Patent number
US05153187

Reaction notes

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