Phosphate → HCID 131717554, compound

HRID 465338Notes

Reaction equation

HRID 465338 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.[CH3:51][N:52]1[CH2:56][C@H:55]([SH:57])[CH2:54][C:53]1=[S:58].P([O-])([O-])([O-])=O>C(#N)C>[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:57][C@H:55]2[CH2:56][N:52]([CH3:51])[C:53](=[S:58])[CH2:54]2)=[O:11])=[CH:25][CH:26]=1)([O-:3])=[O:2]

Participants

7

Reactant 5

HCID 1061PhosphateHCID 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 54409117HCID 54409117, compound

Product 1

HCID 131717554HCID 131717554, compoundYield 68.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2- oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester (25.2 g) is dissolved in anhydrous acetonitrile (173 ml), and thereto are added dropwise diisopropylethylamine (13 ml) and diphenylphosphoryl chloride (15.5 ml) in this order under nitrogen gas below 0° C. After stirring the mixture at the same temperature for 30 minutes, a solution of (4R)-N-methyl-4- mercaptopyrrolidine-2-thione (13 g) and diisopropylethylamine (11.5 g) in anhydrous acetonitrile (173 ml) is added dropwise to the reaction mixture below -5° C. After stirring the mixture at 0° C. for 1.5 hour, the reaction mixture is poured into phosphate buffer (pH 7.0, one liter). The precipitated crystal is separated by filtration and dissolved in a mixture of chloroform (2 liters) and tetrahydrofuran (1 liter), and the solution is washed with water, dried and concentrated to dryness under reduced pressure. The residue is crystallized from diethyl ether to give (1R, 5S, 6S)-2-[(4R)-N-methyl- pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen -2-em-3-carboxylic acid 4-nitrobenzyl ester (23.5 g) as colorless needles.

Workup

  1. stirringAfter stirring the mixture at 0° C. for 1.5 hour
  2. customThe precipitated crystal is separated by filtration
  3. dissolutiondissolved in a mixture of chloroform (2 liters) and tetrahydrofuran (1 liter)
  4. washthe solution is washed with water
  5. customdried
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue is crystallized from diethyl ether

Sources & evidence

ORD record
ord-655a9d6838a245449c15fbc7ea564b3b
Source dataset
uspto-grants-1992_10
Patent number
US05153187

Reaction notes

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