Trifluoroacetic acid → HCID 178525238, compound

HRID 1858521Notes

Reaction equation

HRID 1858521 reaction equation
[C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:43](=[O:44])[N:13]3[C:14]([C:27]([O:29]C(C4C=CC=CC=4)C4C=CC=CC=4)=[S:28])=[C:15]([C:18]4[NH:22][N:21]=[C:20]([CH2:23][C:24]([OH:26])=[O:25])[N:19]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O.C(OC(C)C)(C)C>ClCCl.C1(OC)C=CC=CC=1.C(=O)(O)[O-].[Na+]>[C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:43](=[O:44])[N:13]3[C:14]([C:27]([OH:29])=[S:28])=[C:15]([C:18]4[N:19]=[C:20]([CH2:23][C:24]([OH:26])=[O:25])[NH:21][N:22]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7914Diisopropyl EtherHCID 178525257HCID 178525257, compound

Product 1

HCID 178525238HCID 178525238, compoundYield 9.5%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 7519AnisoleSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of benzhydryl 7β-(2-phenylacetamido)-3-(3-carboxymethyl-1,2,4-triazol-5-yl)thio-3-cephem-4-carboxylate (370 mg) in a mixture of dichloromethane (1.2 ml) and anisole (0.4 ml) was added trifluoroacetic acid (0.8 ml) under ice-cooling. The mixture was stirred at room temperature for 50 minutes. The reaction mixture was poured into diisopropyl ether (30 ml), and the resulting precipitate was collected by filtration and dried in vacuo. The precipitate was dissolved in a mixture of aqueous sodium hydrogen carbonate (58 mg/30 ml), tetrahydrofuran (10 ml) and ethyl acetate (30 ml). To the separated aqueous layer was added tetrahydrofuran (10 ml) and ethyl acetate (30 ml), adjusted to pH 2.0 with 1N-hydrochloric acid. The organic layer was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with isopropyl ether to give crude product (190 mg). The crude product (175 mg) was dissolved in a mixture of aqueous sodium bicarbonate (62 mg/10 ml), purified by high pressure liquid chromatography (HPLC) (R-ODS-C-15, YMC-pack) eluting with 20% acetonitrile-phosphate buffer (pH 3.0). The solution was concentrated in vacuo. To the resulting solution was added tetrahydrofuran (10 ml) and ethyl acetate (40 ml) and adjusted to pH 2.2 with 1N-hydrochloric acid. The organic layer was washed with saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated in vacuo. The residue was triturated with isopropyl ether to give 7β-(2-phenylacetamido)-3-(5-carboxymethyl-1,2,4-triazol-3-yl)thio-3-cephem-4-carboxylic acid (25.7 mg).

Workup

  1. temperaturecooling
  2. filtrationthe resulting precipitate was collected by filtration
  3. customdried in vacuo
  4. dissolutionThe precipitate was dissolved in a mixture of aqueous sodium hydrogen carbonate (58 mg/30 ml), tetrahydrofuran (10 ml) and ethyl acetate (30 ml)
  5. additionTo the separated aqueous layer was added tetrahydrofuran (10 ml) and ethyl acetate (30 ml)
  6. washThe organic layer was washed with saturated aqueous sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was triturated with isopropyl ether
  10. customto give crude product (190 mg)
  11. custompurified by high pressure liquid chromatography (HPLC) (R-ODS-C-15, YMC-pack)
  12. washeluting with 20% acetonitrile-phosphate buffer (pH 3.0)
  13. concentrationThe solution was concentrated in vacuo
  14. additionTo the resulting solution was added tetrahydrofuran (10 ml) and ethyl acetate (40 ml)
  15. washThe organic layer was washed with saturated aqueous sodium chloride
  16. dry with materialdried over magnesium sulfate
  17. concentrationconcentrated in vacuo
  18. customThe residue was triturated with isopropyl ether

Sources & evidence

ORD record
ord-0d8f0756bd184613944805c4cd2bc7ac
Source dataset
uspto-grants-2000_11
Patent number
US06150351

Reaction notes

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