Reaction #436722

Reaction equation

sodium hydrogencarbonate

7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-(3-formamido-4-formamidomethyl-2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate

hydrochloric acid

→

7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-(3-amino-4-aminomethyl-2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate

Yield 2.2%

Solvents

methanol

Conditions

Workup

1. 1
   Concentrationconcentrated in vacuo
2. 2
   Otherto remove methanol
3. 3
   OtherThe resulting residue was purified by preparative HPLC utilizing ODS column
4. 4
   workup.ADDITIONThe eluate containing a desired product
5. 5
   Concentrationwas concentrated to about 30 ml in vacuo
6. 6
   Otherchromatographed on Diaion®
7. 7
   Wash(Mitsubishi Chemical Corporation) eluting with 20% aqueous 2-propanol
8. 8
   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-formamido-4-formamidomethyl-2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate (2.5 g) in methanol (25 ml) was added concentrated hydrochloric acid (2.5 ml) at room temperature. The mixture was stirred at room temperature for 17 hours. The reaction mixture was adjusted to about pH 7 with saturated aqueous sodium hydrogencarbonate solution and concentrated in vacuo to remove methanol. The resulting residue was purified by preparative HPLC utilizing ODS column. The eluate containing a desired product was concentrated to about 30 ml in vacuo. The concentrate was adjusted to about pH 1 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-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate (50 mg) as an amorphous solid.

Source