Hydrochloric Acid → p-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(3S,5S)-1-p-nitrobenzyloxycarbonyl-5-(4-sulfamoylphenylthiomethyl)pyrrolidin-3-ylthio)-1-carbapen-2-em-3-carboxylate

HRID 725934Notes

Reaction equation

HRID 725934 reaction equation
[C:1]([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C@H:7]([CH2:23][S:24][C:25]2[CH:30]=[CH:29][C:28]([S:31](=[O:34])(=[O:33])[NH2:32])=[CH:27][CH:26]=2)[CH2:6]1)(=O)[CH3:2].[OH-:35].[Na+].Cl.C1(P(OC2[C@H](C)[C@H]3[C@@H]([C@H](O)C)C(=O)N3C=2[C:58]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=2)=[O:59])(C2C=CC=CC=2)=O)C=CC=CC=1.[CH3:78][OH:79]>C(#N)C.C(OCC)(=O)C.C(Cl)(Cl)Cl>[OH:35][C@@H:15]([C@H:16]1[C:78](=[O:79])[N:20]2[C:2]([C:58]([O:60][CH2:61][C:62]3[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=3)=[O:59])=[C:1]([S:4][C@H:5]3[CH2:6][C@@H:7]([CH2:23][S:24][C:25]4[CH:30]=[CH:29][C:28]([S:31](=[O:33])(=[O:34])[NH2:32])=[CH:27][CH:26]=4)[N:8]([C:10]([O:12][CH2:13][C:14]4[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=4)=[O:11])[CH2:9]3)[C@H:18]([CH3:19])[C@H:17]12)[CH3:14]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 22881094(2s,4s)-4-Acetylthio-1-p-nitrobenzyloxycarbonyl-2-(4-sulfamoylphenyl)thiomethylpyrrolidineHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131720383p-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(3S,5S)-1-p-nitrobenzyloxycarbonyl-5-(4-sulfamoylphenylthiomethyl)pyrrolidin-3-ylthio)-1-carbapen-2-em-3-carboxylateYield 67%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,4S)-4-acetylthio-1-p-nitrobenzyloxycarbonyl-2-(4-sulfamoylphenyl)thiomethylpyrrolidine (1.48 g, 2.82 mmol) in a mixture of methanol (30 ml) with chloroform (30 ml), 1N aqueous NaOH (3.11 ml, 3.11 mmol) was added in a nitrogen stream at 5° C., and the resulting reaction solution was stirred at the same temperature for 1 hour. The reaction solution was neutralized with 1N aqueous HCl (3.11 ml, 3.11 mmol), and the solvent was distilled off in vacuo. To a solution of the residue and p-nitrobenzyl (1R,5S,6S)-2-diphenylphosphoryloxy-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (2.24 g, 3.78 mmol) in acetonitrile (50 ml), DIPA (0.78 ml, 4.48 mmol) was added, and the reaction solution was stirred at 5° C. overnight. To the reaction solution, ethyl acetate was added. The solution was washed successively with water, 10% aqueous citric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride. Then, it was dried over anhydrous sodium sulfate, and the solvent was distilled off in vacuo. The resulting residue was purified by silica gel column chromatography (heptane-ethyl acetate) to give p-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(3S,5S)-1-p-nitrobenzyloxycarbonyl-5-(4-sulfamoylphenylthiomethyl)pyrrolidin-3-ylthio)-1-carbapen-2-em-3-carboxylate (1.57 g, yield: 67%).

Workup

  1. additionwas added in a nitrogen stream at 5° C.
  2. customthe resulting reaction solution
  3. distillationthe solvent was distilled off in vacuo
  4. stirringthe reaction solution was stirred at 5° C. overnight
  5. washThe solution was washed successively with water, 10% aqueous citric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  6. dry with materialThen, it was dried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off in vacuo
  8. customThe resulting residue was purified by silica gel column chromatography (heptane-ethyl acetate)

Sources & evidence

ORD record
ord-68397ace5aba476aa30628c751d7491c
Source dataset
uspto-grants-1998_01
Patent number
US05707987

Reaction notes

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