Phosphate → (1R, 5S, 6S)-2-[(4R)-N-methylpyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid acetoxymethyl ester

HRID 465339Notes

Reaction equation

HRID 465339 reaction equation
[Na+].[CH3:2][N:3]1[CH2:7][C@H:6]([S:8][C:9]2[C@H:10]([CH3:23])[C@@H:11]3[C@@H:18]([C@H:19]([OH:21])[CH3:20])[C:17](=[O:22])[N:12]3[C:13]=2[C:14]([O-:16])=[O:15])[CH2:5][C:4]1=[S:24].C(=O)([O-])[O-].[K+].[K+].[C:31]([O:34][CH2:35]I)(=[O:33])[CH3:32].P([O-])([O-])([O-])=O>CN(C)C=O>[C:31]([O:34][CH2:35][O:15][C:14]([C:13]1[N:12]2[C:17](=[O:22])[C@H:18]([C@H:19]([OH:21])[CH3:20])[C@H:11]2[C@@H:10]([CH3:23])[C:9]=1[S:8][C@H:6]1[CH2:7][N:3]([CH3:2])[C:4](=[S:24])[CH2:5]1)=[O:16])(=[O:33])[CH3:32]

Participants

6

Reactant 4

HCID 1061PhosphateHCID 11430Potassium CarbonateHCID 11820084Iodomethyl acetateHCID 131717556(1R, 5S, 6S)-2-[(4R)-N-methylpyrrolidine-2-thion-4ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid sodium salt

Product 1

HCID 131717555(1R, 5S, 6S)-2-[(4R)-N-methylpyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid acetoxymethyl esterYield 55.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1R, 5S, 6S)-2-[(4R)-N-methylpyrrolidine-2-thion-4ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid sodium salt (400 mg) is suspended in N,N-dimethylformamide (5 ml), and thereto is added potassium carbonate (146 mg). To the mixture is added acetoxymethyl iodide (275 mg) at 5°-7° C., and the mixture is stirred at the same temperature for one hour. The reaction mixture is poured into phosphate buffer (pH 7.0) and extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (eluent, chloroform - chloroform:ethanol=98:2), followed by crystallization from tetrahydrofuran and diethyl ether to give (1R, 5S, 6S)-2-[(4R)-N-methylpyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid acetoxymethyl ester (250 mg) as colorless needles.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer is washed with water
  3. customdried
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe residue is purified by silica gel column chromatography (eluent, chloroform - chloroform:ethanol=98:2)
  6. customfollowed by crystallization from tetrahydrofuran and diethyl ether

Sources & evidence

ORD record
ord-4f28a8d08fae45c0b1fc84c289a6d0b6
Source dataset
uspto-grants-1992_10
Patent number
US05153187

Reaction notes

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