Reaction #436719

ord-634ce5b286ba410abaa26490ab4468b7

Reaction equation

CCOC(C)=O
ethyl acetate
CC(C)(O/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(C[n+]3cc(CNC=O)c(N)n3CCO)CS[C@H]12)c1nsc(N)n1)C(=O)O
7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-formamidomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate
Cl
hydrochloric acid
→
CC(C)(O/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(C[n+]3cc(CN)c(N)n3CCO)CS[C@H]12)c1nsc(N)n1)C(=O)O
7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-aminomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate
Yield 18.9%

Reactants

CCOC(C)=O
ethyl acetate
CC(C)(O/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(C[n+]3cc(CNC=O)c(N)n3CCO)CS[C@H]12)c1nsc(N)n1)C(=O)O
7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-formamidomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate
Cl
hydrochloric acid

Reagents

None

Solvents

CO
methanol

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    FiltrationThe resulting precipitate was collected by filtration
  2. 2
    Otherdried in vacuo
  3. 3
    workup.DISSOLUTIONThe obtained powder was dissolved in a phosphate buffer (pH 7)
  4. 4
    workup.ADDITIONThe solution containing the objective compound
  5. 5
    Otherwas purified by preparative HPLC utilizing ODS column
  6. 6
    workup.ADDITIONThe eluate containing the desired product
  7. 7
    Concentrationwas concentrated in vacuo
  8. 8
    Otherchromatographed on Diaion®
  9. 9
    Wash(Mitsubishi Chemical Corporation) eluting with 20% aqueous 2-propanol
  10. 10
    ConcentrationThe eluate was concentrated in vacuo

Procedure

To a solution of 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-formamidomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate (97 mg) in methanol (1 ml) was added concentrated hydrochloric acid (0.1 ml) at room temperature. The mixture was stirred at room temperature for 4.5 hours and poured into ethyl acetate. The resulting precipitate was collected by filtration and dried in vacuo. The obtained powder was dissolved in a phosphate buffer (pH 7), and the solution was adjusted to about pH 6 with saturated aqueous sodium hydrogencarbonate solution. The solution containing the objective compound was purified by preparative HPLC utilizing ODS column. The eluate containing the desired product was concentrated in vacuo. The concentrate was adjusted to about pH 2 with concentrated hydrochloric acid and chromatographed on Diaion® HP-20 (Mitsubishi Chemical Corporation) eluting with 20% aqueous 2-propanol. The eluate was concentrated in vacuo and lyophilized to give 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-aminomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate (17.5 mg).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07179801B2uspto-grants-2007_02