Trifluoroacetic acid → 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylic acid

HRID 704269Notes

Reaction equation

HRID 704269 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:45][O:46][CH2:47][C:48]([OH:50])=[O:49])[C:8]([NH:10][CH:11]2[C:43](=[O:44])[N:13]3[C:14]([C:27]([O:29]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:28])=[C:15]([S:18]/[CH:19]=[CH:20]\[C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1.FC(F)(F)C(O)=O.C(OC(C)C)(C)C>C(Cl)Cl.C1(OC)C=CC=CC=1>[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:45][O:46][CH2:47][C:48]([OH:50])=[O:49])[C:8]([NH:10][CH:11]2[C:43](=[O:44])[N:13]3[C:14]([C:27]([OH:29])=[O:28])=[C:15]([S:18]/[CH:19]=[CH:20]\[C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7914Diisopropyl EtherHCID 131716150benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3yl)-2-carboxymethoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate

Product 1

HCID 1317161537-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylic acidYield 22.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7519AnisoleSolvent

Procedure

To a solution of benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate (syn isomer) (1.28 g) in a mixture of methylene chloride (3.8 ml) and anisole (1.28 ml) was added trifluoroacetic acid (2.6 ml) under ice-cooling. The mixture was stirred for 45 minutes at the same temperature The mixture was poured into diisopropyl ether (200 ml) to give a precipitate. The precipitate was collected, washed with diisopropyl ether and dissolved in a mixture of ethyl acetate and dilute aqueous solution of sodium bicarbonate at pH 5. The insoluble material was filtered off. The aqueous layer was separated and concentrated in vacuo in order to remove ethyl acetate. The aqueous solution was adjusted to pH 4.5 with dilute hydrochloric acid, subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (20 ml) and eluted with water. The fractions containing the object compound were combined and concentrated in vacuo to about 20 ml. The concentrated solution was adjusted to pH 2 with dilute hydrochloric acid under ice-cooling to give a precipitate. The precipitate was collected, washed with cold water and dried over phosphorus pentoxide to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylic acid (syn isomer) (220 mg).

Workup

  1. temperaturecooling
  2. customto give a precipitate
  3. customThe precipitate was collected
  4. washwashed with diisopropyl ether
  5. dissolutiondissolved in a mixture of ethyl acetate and dilute aqueous solution of sodium bicarbonate at pH 5
  6. filtrationThe insoluble material was filtered off
  7. customThe aqueous layer was separated
  8. concentrationconcentrated in vacuo in order
  9. customto remove ethyl acetate
  10. washeluted with water
  11. additionThe fractions containing the object compound
  12. concentrationconcentrated in vacuo to about 20 ml
  13. temperaturecooling
  14. customto give a precipitate
  15. customThe precipitate was collected
  16. washwashed with cold water
  17. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-09c202cde5c040a684f324ec341f0f55
Source dataset
uspto-grants-1991_01
Patent number
US04985555

Reaction notes

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