Trifluoroacetic acid → 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acid

HRID 980997Notes

Reaction equation

HRID 980997 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[S:13][N:12]=[C:11]([C:14](=[N:51][O:52][CH2:53][CH3:54])[C:15]([NH:17][CH:18]2[C:49](=[O:50])[N:20]3[C:21]([C:33]([O:35]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:34])=[C:22]([CH:25]=[CH:26][C:27]4[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=4)[CH2:23][S:24][C@H:19]23)=[O:16])[N:10]=1.C1(OC)C=CC=CC=1.C(OC(C)C)(C)C>ClCCl>[NH2:8][C:9]1[S:13][N:12]=[C:11]([C:14](=[N:51][O:52][CH2:53][CH3:54])[C:15]([NH:17][CH:18]2[C:49](=[O:50])[N:20]3[C:21]([C:33]([OH:35])=[O:34])=[C:22]([CH:25]=[CH:26][C:27]4[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=4)[CH2:23][S:24][C@H:19]23)=[O:16])[N:10]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 7914Diisopropyl EtherHCID 131714369Benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylate

Product 1

HCID 1317143707-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acidYield 42.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (18.3 ml) was added to a suspension of benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylate (syn isomer) (cis-trans mixture) (16.4 g) and anisole (10.7 ml) in dichloromethane (65 ml) at ambient temperature and stirred for 1.5 hours at the same temperature. To the reaction mixture was added diisopropyl ether (300 ml) under stirring. The resulting precipitate was collected by filtration and washed with diisopropyl ether. The precipitate was added to a mixture of ethyl acetate (100 ml) and water (300 ml) and the mixture was adjusted to pH 8 with 20% potassium carbonate. The separated aqueous layer was adjusted to pH 3.5 with 10% hydrochloric acid under ice-cooling. The precipitate, whose main component was the disired trans isomer, was filtered off and added to water (300 ml). The solution was adjusted to pH 7.5 with saturated aqueous sodium bicarbonate. After removal of the insoluble substance by filtration, the filterate was adjusted to pH 3.5 with 2N-hydrochloric acid under ice-cooling. The precipitate was filtered, washed with ice-cooled water and dried over phosphorus pentoxide in vacuo to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acid (syn isomer) (trans isomer) (5.2 g). The filtrate and the washings were combined and the resultant solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" and eluted with 30% aqueous solution of isopropyl alcohol. The fraction containing the object compound was concentrated and lyophilized to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acid (syn isomer) (cis isomer) (3.7 g).

Workup

  1. stirringunder stirring
  2. filtrationThe resulting precipitate was collected by filtration
  3. washwashed with diisopropyl ether
  4. additionThe precipitate was added to a mixture of ethyl acetate (100 ml) and water (300 ml)
  5. temperaturecooling
  6. filtrationwas filtered off
  7. additionadded to water (300 ml)
  8. customAfter removal of the insoluble substance
  9. filtrationby filtration
  10. temperaturecooling
  11. filtrationThe precipitate was filtered
  12. washwashed with ice-
  13. temperaturecooled water
  14. dry with materialdried over phosphorus pentoxide in vacuo

Sources & evidence

ORD record
ord-f6816228434e4e10b7e5b2072770021d
Source dataset
uspto-grants-1987_01
Patent number
US04639448

Reaction notes

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