Acetic Acid → 2-Methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 28297Notes

Reaction equation

HRID 28297 reaction equation
[CH3:1][CH:2]1[CH:7]=[C:6]([C:8]([O:10]CC(Cl)(Cl)Cl)=[O:9])[N:5]2[C:16](=[O:31])[CH:17]([NH:18][C:19](=[O:30])[C:20](=[N:27][O:28][CH3:29])[C:21]3[N:22]=[C:23]([NH2:26])[S:24][CH:25]=3)[C@H:4]2[S:3]1.C(O)(=O)C>O1CCCC1.[Zn]>[CH3:1][CH:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[N:5]2[C:16](=[O:31])[CH:17]([NH:18][C:19](=[O:30])[C:20](=[N:27][O:28][CH3:29])[C:21]3[N:22]=[C:23]([NH2:26])[S:24][CH:25]=3)[C@H:4]2[S:3]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 1317114992,2,2-Trichloroethyl 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylateHCID 178502758HCID 178502758, compound

Product 1

HCID 1317114962-Methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,2,2-trichloroethyl 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (syn isomer), which can be represented as 2,2,2-trichloroethyl 2-methyl-7-[2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (syn isomer), (0.1 g.) in tetrahydrofuran (2 ml.) and glacial acetic acid (0.25 ml.) was added zinc powder (0.1 g.) all at once with stirring at keeping the temperature below 25° C. in an ice-bath and then the mixture was stirred for 1 hour at room temperature. To the reaction mixture was further added zinc powder (0.1 g.) and the mixture was stirred for 1 hour at the same temperature. The reaction mixture was filtered, and the insoluble material was washed with a small amount of tetrahydrofuran. After the filtrate and the washing were combined together, the solvents were distilled off. To the residue were added 5% aqueous sodium bicarbonate solution and ethyl acetate so that the aqueous layer became pH 7 to 8, and the mixture was filtered, and then the aqueous layer was separated. The aqueous layer was adjusted to pH 2 to 3 with 2 N hydrochloric acid and then concentrated slightly. Thus obtained aqueous layer was subjected to column chromatography (non-ionic adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries) and the column was washed with water and then eluted with 20% methanol and 40% methanol in turn. The eluates containing the object compound were collected and then lyophilized to give white powder of 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7-[2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (0.015 g.), mp 230° to 235° C. (dec.).

Workup

  1. customthe temperature below 25° C.
  2. stirringthe mixture was stirred for 1 hour at room temperature
  3. stirringthe mixture was stirred for 1 hour at the same temperature
  4. filtrationThe reaction mixture was filtered
  5. washthe insoluble material was washed with a small amount of tetrahydrofuran
  6. distillationthe solvents were distilled off
  7. additionTo the residue were added 5% aqueous sodium bicarbonate solution and ethyl acetate so that the aqueous layer
  8. filtrationthe mixture was filtered
  9. customthe aqueous layer was separated
  10. concentrationconcentrated slightly
  11. customThus obtained aqueous layer was subjected to column chromatography (non-ionic adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries)
  12. washthe column was washed with water
  13. washeluted with 20% methanol and 40% methanol in turn
  14. additionThe eluates containing the object compound
  15. customwere collected

Sources & evidence

ORD record
ord-08496bb476784e4da0d65051105f56e1
Source dataset
uspto-grants-1980_09
Patent number
US04225707

Reaction notes

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