7-Aminocephalosporanic acid → HCID 70455521, compound

HRID 325911Notes

Reaction equation

HRID 325911 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][N:13]2[C:17]([SH:18])=[N:16][N:15]=[N:14]2)[CH2:6][CH2:5]1.CC(O[CH2:23][C:24]1[CH2:33][S:32][C@@H:27]2[C@H:28]([NH2:31])[C:29](=[O:30])[N:26]2[C:25]=1[C:34]([OH:36])=[O:35])=O.C(=O)(O)[O-].[Na+]>O>[NH2:31][CH:28]1[C:29](=[O:30])[N:26]2[C:25]([C:34]([OH:36])=[O:35])=[C:24]([CH2:23][S:18][C:17]3[N:13]([CH2:12][CH2:11][CH2:10][N:7]4[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]4)[N:14]=[N:15][N:16]=3)[CH2:33][S:32][C@H:27]12

Participants

5

Reactant 3

HCID 4413287-Aminocephalosporanic acidHCID 516892Sodium Bicarbonate2×HCID 178480873HCID 178480873, compound

Product 1

HCID 70455521HCID 70455521, compoundYield 34.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
64 °C

Procedure

To a solution of 1-[3-(4-methyl-1-piperazinyl)propyl]-1H-tetrazole-5-thiol.dihydrochloride (75.32 g) in water (6 l) was added 7-aminocephalosporanic acid (60.0 g) and the mixture was adjusted to pH 5.4 with a saturated aqueous solution of sodium bicarbonate and stirred for 2 hours at 64° C. The reaction mixture was cooled and adjusted to pH 6.84 with a saturated aqueous solution of sodium bicarbonate. The resulting mixture was subjected to column chromatography (CM-Cephadex, H-type: 3 l), eluting with water, 0.5% aqueous solution of sodium chloride and 2% aqueous solution of sodium chloride. The fiactions containing the object compound were collected. The resulting mixture (about 7 l) was adjusted to pH 4.5 with a saturated aqueous solution of sodium bicarbonate and then subjected to column chromatography (Non-ion adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries: 3 l) and eluting with water, 2% isopropyl alcohol and 15% isopropyl alcohol. The fractions containing the object compound were collected and then concentrated. The concentrate was lyophilized to give a powder of 7-amino-3-[1-[3-(4-methyl-1-piperazinyl) propyl]-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (34.6 g).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washeluting with water, 0.5% aqueous solution of sodium chloride and 2% aqueous solution of sodium chloride
  3. additionThe fiactions containing the object compound
  4. customwere collected
  5. customsubjected to column chromatography (Non-ion adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries: 3 l)
  6. washeluting with water, 2% isopropyl alcohol and 15% isopropyl alcohol
  7. additionThe fractions containing the object compound
  8. customwere collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-17664b3fa4704e96b19c14998e9043d0
Source dataset
uspto-grants-1984_04
Patent number
US04443443

Reaction notes

Loading…