Trifluoroacetic acid → (6R,7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 619237Notes

Reaction equation

HRID 619237 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[S:10][C:11]([Cl:57])=[C:12](/[C:14](=[N:50]/[O:51]C2CCC=C2)/[C:15]([NH:17][C@@H:18]2[C:48](=[O:49])[N:20]3[C:21]([C:32]([O:34]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:33])=[C:22]([S:25][CH2:26][C:27]4[CH:28]=[N:29][NH:30][CH:31]=4)[CH2:23][S:24][C@H:19]23)=[O:16])[N:13]=1.C1(OC)C=CC=CC=1.C(OC(C)C)(C)C>ClCCl>[NH2:8][C:9]1[S:10][C:11]([Cl:57])=[C:12](/[C:14](=[N:50]/[OH:51])/[C:15]([NH:17][C@@H:18]2[C:48](=[O:49])[N:20]3[C:21]([C:32]([OH:34])=[O:33])=[C:22]([S:25][CH2:26][C:27]4[CH:31]=[N:30][NH:29][CH:28]=4)[CH2:23][S:24][C@H:19]23)=[O:16])[N:13]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 7914Diisopropyl EtherHCID 88198442benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-cyclopent-2-en-1-yloxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 9871187(6R,7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 35.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under nitrogen atmosphere, trifluoroacetic acid (4.0 ml) was added dropwise to a solution of diphenylmethyl 7β-[2-(2-amino-5-chlorothiazol-4-yl)-2-(Z)-(2-cyclopenten-1-yloxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (1.71 g) in the mixture of dichloromethane (6.0 ml) and anisole (2.0 ml) at 0° C. Stirring was continued for 2 hours at the same temperature, the mixture was poured into isopropyl ether (200 ml). The resulting precipitate was collected by filtration, and then dissolved in the mixture of ethyl acetate and pH 6.86 buffer. The organic layer was removed, and the aqueous layer was adjusted pH 3.0 with 1N hydrochloric acid, concentrated in vacuo, then chlomatographed on a HP-20 column (eluent: water-methanol) to afford 7β-[2-(2-amino-5-chlorothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylic acid (418.3 mg).

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. dissolutiondissolved in the mixture of ethyl acetate and pH 6.86 buffer
  3. customThe organic layer was removed
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6da19d62f1a34dd49f51a03d9be7a535
Source dataset
uspto-grants-1999_09
Patent number
US05958914

Reaction notes

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