Formic Acid → 7-[2-(2-aminothiazol-4-yl)-2-(2-aminoethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 1904147Notes

Reaction equation

HRID 1904147 reaction equation
[CH3:1][N:2]1[C:6]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:21](=[O:53])[C:22]([C:28]4[N:29]=[C:30]([NH:33]C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[S:31][CH:32]=4)=[N:23][O:24][CH2:25][CH2:26][NH2:27])[C:18](=[O:54])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:5][N:4]=[N:3]1.C(O)=O.O>Cl>[CH3:1][N:2]1[C:6]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:21](=[O:53])[C:22]([C:28]4[N:29]=[C:30]([NH2:33])[S:31][CH:32]=4)=[N:23][O:24][CH2:25][CH2:26][NH2:27])[C:18](=[O:54])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:5][N:4]=[N:3]1

Participants

5

Reactant 3

HCID 284Formic AcidHCID 962WaterHCID 1317134773-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-7-[2-(2-tritylamino-4-thiazolyl)-2-(2-aminoethoxyimino)-acetamido]-ceph-3-eme-4-carboxylic acid

Product 1

HCID 1317134767-[2-(2-aminothiazol-4-yl)-2-(2-aminoethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A mixture of 2 g of the product of Step B and 5 ml of formic acid was heated with stirring to 40°-45° C. and after the addition of 5 ml of water, the mixture was stirred at 40°-45° C. for 15 minutes and was then cooled. The mixture was vacuum filtered to remove triphenylcarbinol and the filtrate was evaporated to dryness under reduced pressure. The residue was taken up in 10 ml of ethanol with efflorescence and the mixture was vacuum filtered. The recovered product was rinsed with ethanol and then with ether to obtain 1.36 g of raw product which was taken up in 15 ml of 2 N hydrochloric acid. The mixture was vacuum filtered and the filtrate was adjusted to a pH of 4 with 3 ml of an aqueous molar solution of lithium acetate and then with aqueous lithium hydroxide. The mixture was vacuum filtered and the filtrate was evaporated to dryness under reduced pressure. The residue was taken up in 30 ml of ethanol with efflorescence and the mixture was vacuum filtered to obtain 515 mg of syn isomer of 3-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-7-[2-(2-amino-4-thiazolyl)-2-(2-aminoethoxyimino)-acetamido]-ceph-3-eme-4-carboxylic acid. The mother liquors were evaporated to dryness to obtain another 133 mg of the said product and the combined products were treated again in the same manner to obtain a final yield of 430 mg of the product in the form of a white powder.

Workup

  1. temperaturewas heated
  2. stirringthe mixture was stirred at 40°-45° C. for 15 minutes
  3. temperaturewas then cooled
  4. filtrationfiltered
  5. customto remove triphenylcarbinol
  6. customthe filtrate was evaporated to dryness under reduced pressure
  7. filtrationfiltered
  8. washThe recovered product was rinsed with ethanol
  9. customwith ether to obtain 1.36 g of raw product which
  10. filtrationfiltered
  11. filtrationfiltered
  12. customthe filtrate was evaporated to dryness under reduced pressure
  13. filtrationfiltered

Sources & evidence

ORD record
ord-d349d837f9404f0ea6ed5b0cac9330d8
Source dataset
uspto-grants-1984_03
Patent number
US04439433

Reaction notes

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