Sodium Carbonate → 4-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-n-butoxyiminoacetamido]3-cephem-4-carboxylate

HRID 1650503Notes

Reaction equation

HRID 1650503 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:24][CH:25]1[C:45](=[O:46])[N:27]2[C:28]([C:32]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][CH:37]=3)=[O:33])=[CH:29][CH2:30][S:31][C@H:26]12.C(=O)([O-])[O-].[Na+].[Na+]>O.CC(C)=O.O1CCCC1.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:15]([NH:24][CH:25]2[C:45](=[O:46])[N:27]3[C:28]([C:32]([O:34][CH2:35][C:36]4[CH:37]=[CH:38][C:39]([N+:42]([O-:44])=[O:43])=[CH:40][CH:41]=4)=[O:33])=[CH:29][CH2:30][S:31][C@H:26]23)=[O:17])[N:13]=1)=[O:7]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 541324842-(2-Formamidothiazol-4-yl)-2-butoxyiminoacetic acid

Product 1

HCID 1317124564-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-n-butoxyiminoacetamido]3-cephem-4-carboxylateYield 81.8%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Phosphoryl chloride (13.2 g.) was added dropwise to a stirred solution of N,N-dimethylformamide (6.3 g.) and tetrahydrofuran (24.7 ml.) at -5° C., and stirred at the same temperature for 30 minutes. Tetrahydrofuran (120 ml.) and 2-(2-formamidothiazol-4-yl)-2-n-butoxyiminoacetic acid (syn isomer, 19.5 g.) were added to the solution at -5° C., and stirred at the same temperature for 30 minutes. The solution was added dropwise a stirred suspension of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate (24.7 g.), tetrahydrofuran (120 ml.), acetone (60 ml.) and water (60 ml.) at -5° to 5° C. over 15 minutes while adjusting to pH 7 to 7.5 with 20% aqueous solution of sodium carbonate, and then the solution was stirred for 30 minutes. The insoluble substance was filtered off, and a saturated aqueous solution of sodium chloride was added to the filtrate. The solution was extracted with tetrahydrofuran twice. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diisopropyl ether to give 4-nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-n-butoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer, 34.6 g.).

Workup

  1. stirringstirred at the same temperature for 30 minutes
  2. additionThe solution was added dropwise
  3. stirringthe solution was stirred for 30 minutes
  4. filtrationThe insoluble substance was filtered off
  5. additiona saturated aqueous solution of sodium chloride was added to the filtrate
  6. extractionThe solution was extracted with tetrahydrofuran twice
  7. washThe extract was washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-8171bca6a6c8487ebd814f87276bbf77
Source dataset
uspto-grants-1990_05
Patent number
US04923998

Reaction notes

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