Hydrochloric Acid → 7-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacid

HRID 1463157Notes

Reaction equation

HRID 1463157 reaction equation
[NH2:1][CH:2]1[C:17](=[O:18])[N:4]2[C:5]([C:14]([OH:16])=[O:15])=[C:6]([CH2:9]OC(=O)C)[CH2:7][S:8][C@H:3]12.C(=O)(O)[O-].[Na+].CN1CN=C(S)S1.Cl.NC1C(=O)N2C(C(O)=O)=C(CSC3SC(C)=NN=3)CS[C@H]12.[CH3:53][N:54]1[C:58]([SH:59])=[N:57][N:56]=[N:55]1>O.CC(C)=O>[NH2:1][CH:2]1[C:17](=[O:18])[N:4]2[C:5]([C:14]([OH:16])=[O:15])=[C:6]([CH2:9][S:59][C:58]3[N:54]([CH3:53])[N:55]=[N:56][N:57]=3)[CH2:7][S:8][C@H:3]12

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 516892Sodium Bicarbonate2×HCID 113463103-Acetoxymethyl-7-amino-3cephem-4-carboxylic acidHCID 129420347-Amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 178481303HCID 178481303, compoundHCID 178482017HCID 178482017, compound

Product 1

HCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacid

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent2×

Procedure

To a stirred suspension of 7-amino-3-acetoxymethylceph-3-em-4-carboxylic acid (13.5 g., 0.05 mole) in water (100 ml.) and acetone (50 ml.) was added a solution of sodium bicarbonate (9.45 g., 0.113 mole) in water (50 ml.). When a homogeneous solution was obtained, 2-methyl-1,2,4-thiadiazole-5-thiol(10 g., 0.075 mole) was added and the mixture heated at 40°-50° under nitrogen while the pH was adjusted to 7.6 by the addition of a solution of 3N HCl. The pH was maintained at 7.6 and the course of the reaction was followed by removing 0.3 ml. aliquots, adjusting the pH to 3 with 1NHCl, filtering the precipitate, washing it with acetone and then ether and examining it by infra red for the disappearance of the carbonyl absorption. The reaction was complete after 10.5 hours and the whole reaction was worked in the same way as described above for the aliquots. There was thus obtained 7-amino-3-[(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid. In a similar manner, but using an equivalent amount of 1-methyl-1H-tetrazole-5-thiol in place of 2-methyl-1,2,4-thiadiazole- 5-thiol, but making the initial adjustment of pH to 7.6 with sodium bicarbonate, and carrying out the reaction for 5 hours under reflux, there was obtained 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid.

Workup

  1. customWhen a homogeneous solution was obtained
  2. temperaturethe mixture heated at 40°-50° under nitrogen while the pH
  3. temperatureThe pH was maintained at 7.6
  4. customby removing 0.3 ml
  5. filtrationfiltering the precipitate
  6. washwashing it with acetone
  7. customred for the disappearance of the carbonyl absorption
  8. customthe whole reaction
  9. customthe reaction for 5 hours
  10. temperatureunder reflux

Sources & evidence

ORD record
ord-b41d78afed454624ae16b6c563b55de5
Source dataset
uspto-grants-1984_07
Patent number
US04463173

Reaction notes

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