Hydrochloric Acid → (1R,5S,6S)-2-[(2S,4S)-2-(3-Aminoazetidin-1-yl-carbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride

HRID 727711Notes

Reaction equation

HRID 727711 reaction equation
[N+](C1C=CC(COC([NH:12][CH:13]2[CH2:16][N:15]([C:17]([C@@H:19]3[CH2:23][C@H:22]([S:24][C:25]4[C@H:26]([CH3:49])[C@@H:27]5[C@@H:44]([C@H:45]([OH:47])[CH3:46])[C:43](=[O:48])[N:28]5[C:29]=4[C:30]([O:32]CC4C=CC([N+]([O-])=O)=CC=4)=[O:31])[CH2:21][N:20]3C(OCC3C=CC([N+]([O-])=O)=CC=3)=O)=[O:18])[CH2:14]2)=O)=CC=1)([O-])=O.[ClH:65].[H][H]>O1CCCC1.O.[Pd]>[ClH:65].[NH2:12][CH:13]1[CH2:14][N:15]([C:17]([C@@H:19]2[CH2:23][C@H:22]([S:24][C:25]3[C@H:26]([CH3:49])[C@@H:27]4[C@@H:44]([C@H:45]([OH:47])[CH3:46])[C:43](=[O:48])[N:28]4[C:29]=3[C:30]([OH:32])=[O:31])[CH2:21][NH:20]2)=[O:18])[CH2:16]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 109750254-Nitrobenzyl (1R,5S,6S)-2-((2S,4S)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 67881971(1R,5S,6S)-2-[(2S,4S)-2-(3-Aminoazetidin-1-yl-carbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

216 mg of 4-nitrobenzyl (1R,5S,6S)-2-((2S,4S)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-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 (1) above] were dissolved in 10 ml of a 3:2 by volume mixture of tetrahydrofuran and water. 250 mg of a 10% w/w palladium-on-carbon catalyst and 239 μl of 1N aqueous hydrochloric acid were then added to the resulting solution, after which the mixture was hydrogenated at room temperature for 1.5 hours in an atmosphere of hydrogen. At the end of this time, the catalyst was removed by filtration, and the filtrate was washed with diethyl ether. The aqueous phase was then concentrated by evaporation under reduced pressure. The resulting residue was subjected to column chromatography (Cosmosil 75C18 -prep, manufactured by Nacalai Tesque, 18 ml). Of the fractions obtained by elution with water, the one containing the title compound was concentrated by evaporation under reduced pressure and freeze-dried to give 46 mg of the title compound as a powder.

Workup

  1. customAt the end of this time, the catalyst was removed by filtration
  2. washthe filtrate was washed with diethyl ether
  3. concentrationThe aqueous phase was then concentrated by evaporation under reduced pressure
  4. customOf the fractions obtained by elution with water
  5. concentrationthe one containing the title compound was concentrated by evaporation under reduced pressure
  6. customfreeze-dried

Sources & evidence

ORD record
ord-83e45c00dd7e460bb9d17a4da56455ad
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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