Methanol → 7-[2-(2-Formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 568855Notes

Reaction equation

HRID 568855 reaction equation
[CH:1]([NH:3][C:4]1[S:5][C:6]([Br:38])=[C:7]([C:9](=[N:35][O:36][CH3:37])[C:10]([NH:12][CH:13]2[C:33](=[O:34])[N:15]3[C:16]([C:20]([O:22]CC4C=CC([N+]([O-])=O)=CC=4)=[O:21])=[CH:17][CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=[O:2].O1CCCC1.CO>[Pd].C(O)(=O)C>[CH:1]([NH:3][C:4]1[S:5][C:6]([Br:38])=[C:7]([C:9](=[N:35][O:36][CH3:37])[C:10]([NH:12][CH:13]2[C:33](=[O:34])[N:15]3[C:16]([C:20]([OH:22])=[O:21])=[CH:17][CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=[O:2]

Participants

6

Reactant 3

HCID 887MethanolHCID 8028TetrahydrofuranHCID 1317153594-Nitrobenzyl 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate

Product 1

HCID 1317153607-[2-(2-Formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acidYield 38.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

4-Nitrobenzyl 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer, 2.65 g.) was add to a mixture of tetrahydrofuran (110 ml.) and methanol (80 ml.). To the solution was added a suspension of 10% palladium on carbon (1.5 g.) in acetic acid (10 ml.) and the mixture was subjected to catalytic hydrolysis at room temperature under ordinal pressure. The reaction mixture was filtered and washed with tetrahydrofuran. The filtrate and washings were combined and evaporated in vacuo. Ethyl acetate was added to the residue, adjusted to pH 7.5 with saturated aqueous sodium bicarbonate and filtered. The aqueous layer was separated and washed with ethyl acetate. 100 ml. of 20% Isopropyl alcohol in ethyl acetate was added to the aqueous solution and adjusted to pH 2.0 with 6N-hydrochloric acid. The mixture was saturated with sodium chloride and the organic layer was separated. The remaining aqueous layer was extracted with a mixture (100 ml. and 50 ml.) of ethyl acetate and isopropyl alcohol (4:1). The organic layer and the extracts were combined, washed with a small amount of saturated aqueous sodium chloride, dried over magnesium sulfate, treated with activated charcoal and then evaporated in vacuo. The residue was pulverized with diisopropyl ether and the precipitates were collected by filtration, washed with diisopropyl ether and dried to give 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.8 g.).

Workup

  1. additionTo the solution was added
  2. customthe mixture was subjected to catalytic hydrolysis at room temperature under ordinal pressure
  3. filtrationThe reaction mixture was filtered
  4. washwashed with tetrahydrofuran
  5. customevaporated in vacuo
  6. additionEthyl acetate was added to the residue
  7. filtrationfiltered
  8. customThe aqueous layer was separated
  9. washwashed with ethyl acetate
  10. additionof 20% Isopropyl alcohol in ethyl acetate was added to the aqueous solution
  11. customthe organic layer was separated
  12. extractionThe remaining aqueous layer was extracted with a mixture (100 ml. and 50 ml.) of ethyl acetate and isopropyl alcohol (4:1)
  13. washwashed with a small amount of saturated aqueous sodium chloride
  14. dry with materialdried over magnesium sulfate
  15. additiontreated with activated charcoal
  16. customevaporated in vacuo
  17. filtrationthe precipitates were collected by filtration
  18. washwashed with diisopropyl ether
  19. customdried

Sources & evidence

ORD record
ord-7b1be7fd323b41bfa58764a326715124
Source dataset
uspto-grants-1988_03
Patent number
US04729991

Reaction notes

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