Acetic Acid → HCID 23388242, compound

HRID 989878Notes

Reaction equation

HRID 989878 reaction equation
C(O)(=O)C.O[C@@H]([C@H]1C(=O)N2C(C([O-])=O)=C(C3SC4=C(C(=O)CC)N=CN4C=3)[C@H](C)[C@H]12)C.[Na+].[Si]([NH:40][S:41]([C:44]1[N:45]=[CH:46][N:47]2[CH:51]=[C:50]([C:52]3[C@H:53]([CH3:76])[C@@H:54]4[C@@H:71]([C@H:72]([OH:74])[CH3:73])[C:70](=[O:75])[N:55]4[C:56]=3[C:57]([O:59][CH2:60][C:61]3[CH:66]=[CH:65][C:64]([N+:67]([O-:69])=[O:68])=[CH:63][CH:62]=3)=[O:58])[S:49][C:48]=12)(=[O:43])=[O:42])(C(C)(C)C)(C)C.C(=O)([O-])O.[Na+]>C1COCC1>[OH:74][C@@H:72]([C@H:71]1[C:70](=[O:75])[N:55]2[C:56]([C:57]([O:59][CH2:60][C:61]3[CH:62]=[CH:63][C:64]([N+:67]([O-:69])=[O:68])=[CH:65][CH:66]=3)=[O:58])=[C:52]([C:50]3[S:49][C:48]4=[C:44]([S:41](=[O:43])(=[O:42])[NH2:40])[N:45]=[CH:46][N:47]4[CH:51]=3)[C@H:53]([CH3:76])[C@H:54]12)[CH3:73]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 23388221HCID 23388221, compoundHCID 23698547HCID 23698547, compound

Product 1

HCID 23388242HCID 23388242, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acetic acid (0.26 ml) and 1.5 ml of a 1 M-tetra-n-butylammonium fluoride/THF solution were added under ice cooling to a solution of 197 mg of 4-nitrobenzyl(1S,5R,6S)-2-(7-t-butyldimethylsilylsulfamoylimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in 6 ml of THF. The solution was stirred at room temperature for 3 hr. The reaction mixture was added to an aqueous sodium hydrogencarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1) to give a crude product of 4-nitrobenzyl(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-sulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate. The crude product was dissolved in 5 ml of THF and 5 ml of 1/15 M sodium phosphate buffer (pH 6.6). 10%Pd—C (50 mg) was added thereto. The atmosphere in the reactor was replaced with hydrogen. The system was stirred at room temperature for 30 min. The catalyst was removed by filtration through Celite, followed by washing with water. The filtrate was adjusted to pH 7.0 by the addition of an aqueous sodium hydrogencarbonate solution, and washed with ethyl acetate. Purification was then carried out using Cosmosil 40C18-PREP (30% aqueous methanol) and Dowex 50 (sodium form) in that order to give 40.7 mg of the title compound.

Workup

  1. extractionfollowed by extraction with dichloromethane
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. customThe solvent was removed by distillation
  4. customThe residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-449c94c4065d454dbb8a0db11c9a7c0d
Source dataset
uspto-grants-2002_10
Patent number
US06458780B1

Reaction notes

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