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

HRID 992697Notes

Reaction equation

HRID 992697 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:44]/[O:45]C(=O)C)/[C:8]([NH:10][C@@H:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:27])=[C:15]([S:18][CH2:19][C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.FC(F)(F)C(O)=O>ClCCl.C1(OC)C=CC=CC=1>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:44]/[OH:45])/[C:8]([NH:10][C@@H:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([OH:28])=[O:27])=[C:15]([S:18][CH2:19][C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 88178984benzhydryl (6R,7R)-7-[[(2Z)-2-acetyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-8-oxo-3-(pyridin-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 10458367(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(pyridin-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 17.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7519AnisoleSolvent

Procedure

To a suspension of diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetamido]-3-[(4-pyridyl)methylthio]-3-cephem-4-carboxylate (2.37 g, 3.51 m mol) in a mixture of dichloromethane (12 ml) and anisole (2.4 ml) was added trifluoroacetic acid (4.8 ml) at 5° C. and the mixture was stirred at the same temperature for 2 hours. The mixture was poured into IPE (300 ml) and the precipitates were collected by filtration, washed with IPE and dried in vacuo. The powder was suspended in a mixture of water (150 ml) and methanol (7.5 ml), and ammonium chloride (563 mg, 10.5 m mol) was added thereto. The mixture was stirred at room temperature with keeping the pH to 8 by addition of saturated NaHCO3 aqueous solution. The mixture was adjusted to pH ca. 6 by addition of 6N HCl and by evaporated in vacuo. The residue was adjusted to pH 3.5 by addition of 6N HCl and chromatographed on HP-20 (80 ml) and eluted with 5% aqueous IPA. The eluent was lyophilized and the crude product was purified by preparative HPLC to give 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(4-pyridyl)methylthio]-3-cephem-4-carboxylic acid (295 mg).

Workup

  1. additionThe mixture was poured into IPE (300 ml)
  2. filtrationthe precipitates were collected by filtration
  3. washwashed with IPE
  4. customdried in vacuo
  5. additionThe powder was suspended in a mixture of water (150 ml) and methanol (7.5 ml), and ammonium chloride (563 mg, 10.5 m mol)
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature
  8. additionby addition of saturated NaHCO3 aqueous solution
  9. additionThe mixture was adjusted to pH ca. 6 by addition of 6N HCl
  10. customby evaporated in vacuo
  11. additionThe residue was adjusted to pH 3.5 by addition of 6N HCl
  12. customchromatographed on HP-20 (80 ml)
  13. washeluted with 5% aqueous IPA
  14. customthe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-3d043b000dd841be9770cc7aec33f688
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

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