Dimethylformamide → (1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester

HRID 465337Notes

Reaction equation

HRID 465337 reaction equation
[K+].[NH:2]1[CH2:6][C@H:5]([S:7][C:8]2[C@H:9]([CH3:22])[C@@H:10]3[C@@H:17]([C@H:18]([OH:20])[CH3:19])[C:16](=[O:21])[N:11]3[C:12]=2[C:13]([O-:15])=[O:14])[CH2:4][C:3]1=[S:23].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[C:35]([O:40][CH2:41]I)(=[O:39])[CH:36]([CH3:38])[CH3:37]>C(OCC)(=O)C>[C:35]([O:40][CH2:41][O:14][C:13]([C:12]1[N:11]2[C:16](=[O:21])[C@H:17]([C@H:18]([OH:20])[CH3:19])[C@H:10]2[C@@H:9]([CH3:22])[C:8]=1[S:7][C@H:5]1[CH2:6][NH:2][C:3](=[S:23])[CH2:4]1)=[O:15])(=[O:39])[CH:36]([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 10376456iodoMethyl 2-MethylpropanoateHCID 131717553(1R, 5S, 6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid potassium salt

Product 1

HCID 9955020(1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl esterYield 30.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (1R, 5S, 6S)-2-[(4R)-pyrrolidine-2- thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2- em-3-carboxylic acid potassium salt (0.34 g), N,N-dimethylformamide (3 ml) and potassium carbonate (0.12 g) is added dropwise isobutyryloxymethyl iodide (0.27 g) under ice cooling. After stirring the mixture at the same temperature for 30 minutes, ethyl acetate (10 ml) is added to the reaction mixture, and the mixture is washed with water, and the organic layer is dried and evaporated under reduced pressure to remove the solvent. The residue is purified by silica gel flash column chromatography (eluent, chloroform: ethanol=20:1), followed by crystallization from isopropyl ether and ethyl acetate to give (1R, 5S, 6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester (0.12 g) as colorless needles.

Workup

  1. washthe mixture is washed with water
  2. customthe organic layer is dried
  3. customevaporated under reduced pressure
  4. customto remove the solvent
  5. customThe residue is purified by silica gel flash column chromatography (eluent, chloroform: ethanol=20:1)
  6. customfollowed by crystallization from isopropyl ether and ethyl acetate

Sources & evidence

ORD record
ord-0077f6b3fd504099ae3ffac10bcbd483
Source dataset
uspto-grants-1992_10
Patent number
US05153187

Reaction notes

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