4-nitrobenzyl (1R, 5S, 6S)-2-[(2S, 4S)-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate → (1R, 5S, 6S)-2-[(2S, 4S)-2-(4-Acetimidoylpiperazin-1-ylcarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

HRID 361995Notes

Reaction equation

HRID 361995 reaction equation
[N+](C1C=CC(COC([N:12]=[C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C@@H:23]3[CH2:27][C@H:26]([S:28][C:29]4[C@H:30]([CH3:53])[C@@H:31]5[C@@H:48]([C@H:49]([OH:51])[CH3:50])[C:47](=[O:52])[N:32]5[C:33]=4[C:34]([O:36]CC4C=CC([N+]([O-])=O)=CC=4)=[O:35])[CH2:25][N:24]3C(OCC3C=CC([N+]([O-])=O)=CC=3)=O)=[O:22])[CH2:17][CH2:16]2)[CH3:14])=O)=CC=1)([O-])=O>O1CCCC1.O>[C:13]([N:15]1[CH2:16][CH2:17][N:18]([C:21]([C@@H:23]2[CH2:27][C@H:26]([S:28][C:29]3[C@H:30]([CH3:53])[C@@H:31]4[C@@H:48]([C@H:49]([OH:51])[CH3:50])[C:47](=[O:52])[N:32]4[C:33]=3[C:34]([OH:36])=[O:35])[CH2:25][NH:24]2)=[O:22])[CH2:19][CH2:20]1)(=[NH:12])[CH3:14]

Participants

4

Reactant 1

HCID 1317204064-nitrobenzyl (1R, 5S, 6S)-2-[(2S, 4S)-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Product 1

HCID 9956142(1R, 5S, 6S)-2-[(2S, 4S)-2-(4-Acetimidoylpiperazin-1-ylcarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acidYield 23.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

114 mg of 4-nitrobenzyl (1R, 5S, 6S)-2-[(2S, 4S)-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate [prepared as described in step (a) above] were dissolved in 6 ml of a 2:1 by volume mixture of tetrahydrofuran and water, and were hydrogenated by bubbling hydrogen through it at room temperature for 2 hours in the presence of 300 mg of 10% w/w palladium-on-charcoal. At the end of this time, the catalyst was filtered off and the filtrate was washed with diethyl ether. The resulting solution was concentrated by evaporation under reduced pressure, and the residue was purified by reverse phase column chromatography through 5 ml of Cosmo Sil 75C18 -PREP (a trade mark for a product of Nacalai Tesque), using 20% v/v aqueous methanol as the eluent. Those fractions containing the title compound were combined, concentrated by evaporation under reduced pressure, and lyophilized, to give 13 mg of the title compound as a powder.

Workup

  1. customby bubbling hydrogen through it at room temperature for 2 hours in the presence of 300 mg of 10% w/w palladium-on-charcoal
  2. filtrationAt the end of this time, the catalyst was filtered off
  3. washthe filtrate was washed with diethyl ether
  4. concentrationThe resulting solution was concentrated by evaporation under reduced pressure
  5. customthe residue was purified by reverse phase column chromatography through 5 ml of Cosmo Sil 75C18 -PREP (a trade mark for a product of Nacalai Tesque),
  6. additionThose fractions containing the title compound
  7. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-7af86fb28e55466bb49ea62b11496bb1
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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