Formic Acid → 7-(2-Methoxyimino-3,3-ethylenedioxybutyramido)-3-methylenecepham-4-carboxylic acid

HRID 463399Notes

Reaction equation

HRID 463399 reaction equation
C(O)=O.O1CCCC1.O.[CH3:10][O:11][N:12]=[C:13]([C:40]1([O:45][CH2:44][CH2:43][O:42]1)[CH3:41])[C:14]([NH:16][CH:17]1[C:38](=[O:39])[N:19]2[C:20]([C:35]([OH:37])=[O:36])=[C:21]([CH2:24]SC3SC4C=CC=CC=4N=3)[CH2:22][S:23][C@H:18]12)=[O:15]>CN(C)C=O.[Zn]>[CH3:10][O:11][N:12]=[C:13]([C:40]1([O:45][CH2:44][CH2:43][O:42]1)[CH3:41])[C:14]([NH:16][CH:17]1[C:38](=[O:39])[N:19]2[CH:20]([C:35]([OH:37])=[O:36])[C:21](=[CH2:24])[CH2:22][S:23][C@H:18]12)=[O:15]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 962WaterHCID 8028TetrahydrofuranHCID 1317125267-(2-Methoxyimino-3,3-ethylenedioxybutyramido)-3-(benzothiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317125257-(2-Methoxyimino-3,3-ethylenedioxybutyramido)-3-methylenecepham-4-carboxylic acidYield 35.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6228DimethylformamideSolvent

Procedure

Formic acid (10 ml.), tetrahydrofuran (40 ml.) and water (10 ml.) were added to a solution of 7-[2-methoxyimino-3,3-ethylenedioxybutyramido]-3-(benzothiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2 g.) in N,N-dimethylformamide (10 ml.). Zinc powder (1.4 g.) was added to the stirred mixture at 0° to 2° C., and stirred at the same temperature for 1.5 hours. The reaction mixture was filtered, and the residue was washed with tetrahydrofuran. The filtrate and the washings were combined and concentrated in vacuo. The residue was diluted with water (50 ml.) and extracted with ethyl acetate (150 ml.). The extract was washed with water and extracted with an aqueous solution of sodium bicarbonate. Ethyl acetate (50 ml.) was added to the extract and acidified to pH 2.0 with 6N hydrochloric acid. After the organic layer was separated, the aqueous layer was extracted with ethyl acetate (50 ml.). The ethyl acetate layers were combined, washed with water and saturated aqueous sodium chloride in turn, dried over magnesium sulfate and evaporated in vacuo. n-Hexane was added to the oily residue and the mixture was allowed to stand in a refrigerator overnight, and triturated. The precipitates were collected by filtration to give a mixture (0.5 g.) of 7-(2-methoxyimino-3,3-ethylenedioxybutyramido)-3-methylenecepham-4-carboxylic acid (syn isomer) and 7-(2-methoxyimino-3,3-ethylenedioxybutyramido)-3-methyl-3-cephem-4-carboxylic acid (syn isomer) (5:1).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe residue was washed with tetrahydrofuran
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with water (50 ml.)
  5. extractionextracted with ethyl acetate (150 ml.)
  6. washThe extract was washed with water
  7. extractionextracted with an aqueous solution of sodium bicarbonate
  8. additionEthyl acetate (50 ml.) was added to the
  9. extractionextract
  10. customAfter the organic layer was separated
  11. extractionthe aqueous layer was extracted with ethyl acetate (50 ml.)
  12. washwashed with water and saturated aqueous sodium chloride in turn
  13. dry with materialdried over magnesium sulfate
  14. customevaporated in vacuo
  15. additionn-Hexane was added to the oily residue
  16. customto stand in a refrigerator overnight
  17. customtriturated
  18. filtrationThe precipitates were collected by filtration

Sources & evidence

ORD record
ord-a0e98db52b924a86aa518a6d76f81187
Source dataset
uspto-grants-1985_05
Patent number
US04518774

Reaction notes

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