Phosphate → (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(6-methylimidazo[5,1-b]thiazolium-3-yl)-1-carbapen-2-em-3-carboxylate

HRID 382626Notes

Reaction equation

HRID 382626 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:31](=[O:32])[N:6]2[C:7]([C:18]([O:20]CC3C=CC([N+]([O-])=O)=CC=3)=[O:19])=[C:8]([C:10]3[N:11]4[CH:17]=[N:16][CH:15]=[C:12]4[S:13][CH:14]=3)[CH2:9][C@H:5]12)[CH3:3].I[CH3:34].P([O-])([O-])([O-])=O>ClCCl.C1COCC1.[Pd]>[OH:1][C@@H:2]([C@H:4]1[C:31](=[O:32])[N:6]2[C:7]([C:18]([O-:20])=[O:19])=[C:8]([C:10]3[N+:11]4[C:12](=[CH:15][N:16]([CH3:34])[CH:17]=4)[S:13][CH:14]=3)[CH2:9][C@H:5]12)[CH3:3]

Participants

7

Reactant 3

HCID 1061PhosphateHCID 6328Methyl iodideHCID 1317229034-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

Product 1

HCID 178462294(5R,6S)-6-((1R)-1-hydroxyethyl)-2-(6-methylimidazo[5,1-b]thiazolium-3-yl)-1-carbapen-2-em-3-carboxylate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 100 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate in 1.5 ml of dry dichloromethane was added 1.37 ml of iodomethane, and the mixture was stirred under the atmosphere of argon in the darkness at room temperature for 24 hours. Unreacted reagent was removed under reduced pressure. The residue thus obtained was dissolved in 4 ml of THF and 4 ml of 1/15 M phosphate buffer (pH 6.8), and 160 mg of 10% Pd-C was added. The reactor was purged with hydrogen, the reaction mixture was stirred at room temperature for 3.5 hours. The catalyst was collected by filtration on Celite and washed with water. The filtrate was washed with ethyl acetate, and purified by column chromatography on DIAION HP-20 and COSMOSEAL 40C18-PREP (water:methanol=20:1) to give 4.8 mg of the title compound.

Workup

  1. customwas removed under reduced pressure
  2. customThe residue thus obtained
  3. customThe reactor was purged with hydrogen
  4. stirringthe reaction mixture was stirred at room temperature for 3.5 hours
  5. filtrationThe catalyst was collected by filtration on Celite
  6. washwashed with water
  7. washThe filtrate was washed with ethyl acetate
  8. custompurified by column chromatography on DIAION HP-20 and COSMOSEAL 40C18-PREP (water:methanol=20:1)

Sources & evidence

ORD record
ord-ed90a141c07745dc8eb3b34c7222537b
Source dataset
uspto-grants-2001_10
Patent number
US06310056B1

Reaction notes

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