Sodium hydrosulfide → Diphenylmethyl 7beta-formamido-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate

HRID 992686Notes

Reaction equation

HRID 992686 reaction equation
[SH-:1].[Na+].C(N(C(C)C)CC)(C)C.[CH:12]([NH:14][C@@H:15]1[C:43](=[O:44])[N:17]2[C:18]([C:27]([O:29][CH:30]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[O:28])=[C:19](OS(C)(=O)=O)[CH2:20][S:21][C@H:16]12)=[O:13].C(=O)=O.ClC(Cl)(Cl)Cl.Cl.Cl[CH2:55][C:56]1[CH:57]=[N:58][NH:59][CH:60]=1>CN(C=O)C.C(OCC)(=O)C.O>[CH:12]([NH:14][C@@H:15]1[C:43](=[O:44])[N:17]2[C:18]([C:27]([O:29][CH:30]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:28])=[C:19]([S:1][CH2:55][C:56]3[CH:57]=[N:58][NH:59][CH:60]=3)[CH2:20][S:21][C@H:16]12)=[O:13]

Participants

9

Reactant 5

HCID 28015Sodium hydrosulfideHCID 81531Diisopropylethylamine2×HCID 10863874Diphenylmethyl 7beta-formamido-3-methanesulfonyloxy-3-cephem-4-carboxylateHCID 184115924-(chloromethyl)-1H-pyrazole hydrochlorideHCID 86602444Carbontetrachloride dry-ice

Product 1

HCID 88158715Diphenylmethyl 7beta-formamido-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylateYield 117%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen atmosphere, the mixture of 440 mg of sodium hydrosulfide and 1.3 ml of diisopropylethylamine in DMF (10 ml) was added to a solution of diphenylmethyl 7β-formamido-3-methanesulfonyloxy-3-cephem-4-carboxylate (2.44 g) in DMF (15 ml) with dry ice-tetrachloromethane cooling. Stirring was continued for 30 minutes, 918 mg of 4-chloromethylpyrazole hydrochloride and 1.04 ml of diisopropylethylamine was added successively to the solution. The whole mixture was stirred for 1 hour, and then poured into a mixture of water and ethyl acetate. Organic layer was separated, and washed with diluted hydrochloric acid and brine, successively, and dried over magnesium sulfate. After evaporation of the solvent, the residue was purified on silica gel (eluent: dichloromethane-acetone) to afford diphenylmethyl 7β-formamido-3-[(pyrazol-4-yl)-methylthio]-3-cephem-4-carboxylate (2.96 g).

Workup

  1. stirringThe whole mixture was stirred for 1 hour
  2. customOrganic layer was separated
  3. washwashed with diluted hydrochloric acid and brine
  4. dry with materialsuccessively, and dried over magnesium sulfate
  5. customAfter evaporation of the solvent
  6. customthe residue was purified on silica gel (eluent: dichloromethane-acetone)

Sources & evidence

ORD record
ord-ba47e967e9d0474292ffaed60342dd31
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

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