Trifluoroacetic acid → 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate

HRID 1609652Notes

Reaction equation

HRID 1609652 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:38][O:39][CH3:40])[C:8]([NH:10][C@@H:11]2[C:36](=[O:37])[N:13]3[C:14]([C:20]([O:22]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:21])=[C:15]([CH2:18][Cl:19])[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1.C1(OC)C=CC=CC=1.[F:49][C:50]([F:55])([F:54])[C:51]([OH:53])=[O:52].C(OC(C)C)(C)C>ClCCl>[F:49][C:50]([F:55])([F:54])[C:51]([OH:53])=[O:52].[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:38][O:39][CH3:40])[C:8]([NH:10][CH:11]2[C:36](=[O:37])[N:13]3[C:14]([C:20]([OH:22])=[O:21])=[C:15]([CH2:18][Cl:19])[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 7914Diisopropyl EtherHCID 131718937Benzhydryl 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

Product 1

HCID 1317172697-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of benzhydryl 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (1.47 g), dichloromethane (5 ml) and anisole (1.4 ml) was added trifluoroacetic acid (5 ml) under ice-cooling with stirring. After being stirred for 30 minutes at the same temperature, the mixture was poured into diisopropyl ether (100 ml). The resulting precipitate was collected by filtration, washed with diisopropyl ether and dried under reduced pressure to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate (syn isomer). This compound was dissolved in N,N-dimethylformamide (15 ml). To the solution was added 2-(N,N-dimethylamino)methyl-5-hydroxy-4-pyridone (1.24 g) . After being stirred for 5 hours at ambient temperature, the reaction mixture was poured into ethyl acetate (100 ml). The resulting precipitate was collected by filtration, washed with ethyl acetate. The precipitate was suspended in water (100 ml) and the suspension was adjusted to pH 2.0 with diluted hydrochloric acid. After removal of insoluble material by filtration, the aqueous solution was subjected to column chromatography on Diaion HP-20 [Trademark: prepared by Mitsubishi Chemical Industries]. The column was washed with water and the elution was carried out with 30% aqueous methanol. The fractions containing desired product were combined and methanol was evaporated in vacuo. The resulting aqueous layer was lyophilized to give 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl )methyl}ammonio]methyl-3-cephem-4-carboxylate (syn isomer) (0.28 g) as a powder.

Workup

  1. temperaturecooling
  2. stirringAfter being stirred for 30 minutes at the same temperature
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with diisopropyl ether
  5. customdried under reduced pressure

Sources & evidence

ORD record
ord-6277b5d9042c45db8edc1d41a2a641c3
Source dataset
uspto-grants-1995_03
Patent number
US05401734

Reaction notes

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