Pyridine → 7-Amino-3-cephem-4-carboxylic acid

HRID 648460Notes

Reaction equation

HRID 648460 reaction equation
C1(CC([NH:10][C@@H:11]2[C:21](=[O:22])[N:13]3[C:14]([C:18]([OH:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=O)C=CC=CC=1.C[Si](C)(C)Cl.N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)Cl.C(N(CC)CC)C.O.CO>[NH2:10][C@@H:11]1[C:21](=[O:22])[N:13]2[C:14]([C:18]([OH:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]12

Participants

9

Reactant 4

HCID 1049Pyridine2×HCID 6397ChlorotrimethylsilaneHCID 24819Phosphorus pentachlorideHCID 13193156Ceftizoxime Impurity 46

Product 1

HCID 117357907-Amino-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

A solution of 0.955 g of 7β-(N-phenylacetyl-amino)ceph-3-em-4-carboxylic acid in 60 ml of absolute methylene chloride is treated with 0.720 g of trimethylchlorosilane and 0.474 g of absolute pyridine. The mixture is stirred for 60 minutes at room temperature and then cooled to -20° C., and a solution of 3.20 g of absolute pyridine in 30 ml of absolute methylene chloride, and 23.4 ml of an 8% solution of phosphorus pentachloride in absolute methylene chloride, are then added successively. The mixture is stirred for 60 minutes at -10° C. to -12° C. and is again cooled to about -20° C., and 15 ml of absolute methanol are then allowed to run in. The whole is stirred for 25 minutes at -10° C. and then for 35 minutes at room temperature, 15 ml of water are added, the pH value of the reaction mixture is increased from 1.8 to 2.2 by dropwise addition of triethylamine and the mixture is stirred for 20 minutes at room temperature. The pH value is raised to 3.8 by renewed addition of triethylamine and the two-phase mixture is stirred for 90 minutes whilst cooling in an ice bath and is then filtered. The filter residue is washed with methanol, methylene chloride and diethyl ether and is dried in a vacuum desiccator. 7β-amino-ceph-3-em-4-carboxylic acid of the formula ##STR27## is thus obtained in an amorphous form; the product is further processed without purification.

Workup

  1. temperaturecooled to -20° C.
  2. stirringThe mixture is stirred for 60 minutes at -10° C. to -12° C.
  3. temperatureis again cooled to about -20° C.
  4. stirringThe whole is stirred for 25 minutes at -10° C.
  5. waitfor 35 minutes at room temperature
  6. stirringthe mixture is stirred for 20 minutes at room temperature
  7. temperatureThe pH value is raised to 3.8
  8. stirringthe two-phase mixture is stirred for 90 minutes
  9. temperaturewhilst cooling in an ice bath
  10. filtrationis then filtered
  11. washThe filter residue is washed with methanol, methylene chloride and diethyl ether
  12. customis dried in a vacuum desiccator

Sources & evidence

ORD record
ord-ef5af39cf8a446e8b726586171b61c06
Source dataset
uspto-grants-1988_04
Patent number
US04735937

Reaction notes

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