Hydrochloric Acid → Diphenylmethyl 7beta-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate

HRID 992689Notes

Reaction equation

HRID 992689 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.C1(CC([NH:16][C@@H:17]2[C:66](=[O:67])[N:19]3[C:20]([C:50]([O:52][CH:53]([C:60]4[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)=[O:51])=[C:21]([S:24][CH2:25][C:26]4[CH:27]=[N:28][N:29](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[CH:30]=4)[CH2:22][S:23][C@H:18]23)=O)C=CC=CC=1.Cl.[OH-].[Na+]>ClCCl.C(OCC)(=O)C.O.CO.N1C=CC=CC=1>[NH2:16][C@@H:17]1[C:66](=[O:67])[N:19]2[C:20]([C:50]([O:52][CH:53]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=3)=[O:51])=[C:21]([S:24][CH2:25][C:26]3[CH:30]=[N:29][NH:28][CH:27]=3)[CH2:22][S:23][C@H:18]12

Participants

10

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 24819Phosphorus pentachlorideHCID 70122618Diphenylmethyl 7beta-phenylacetamido-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate

Product 1

HCID 70122266Diphenylmethyl 7beta-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylateYield 54.1%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

Pyridine (1.3 ml) was added to a suspension of phosphorus pentachloride (3.37 g) in dichloromethane (47.6 ml) at −10° C., and the mixture was stirred at between −15 to −5° C. for 30 minutes. Diphenylmethyl 7β-phenylacetamido-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (6.8 g) was added to the above mixture at −10° C. and the reaction mixture was stirred under ice-cooling for 1 hour. Then, methanol (5.2 ml) was added to the reaction mixture at −20° C. and the resulting solution was stirred under ice-cooling for 1 hour. Water (40 ml) was added to the above mixture under ice-cooling, and stirred for 30 minutes at the same temperature. The aqueous layer was separated and the dichloromethane layer was reextracted with 1 mol hydrochloric acid (30 ml). The aqueous layer and 1 mol hydrochloric acid layer were combined ethyl acetate (50 ml) was added to the aqueous layer and then the mixture was adjusted to pH 3.5 with 30% aqueous sodium hydroxide under stirring. The organic layer was separated, washed with brine (20 ml) and dried over magnesium sulfate. The solvent was distilled off and the residue was pulverized with IPE (50 ml), collected by filtration, washed with IPE (20 ml) and dried over phosphorus pentoxide to give powder of diphenylmethyl 7β-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (2.1 g).

Workup

  1. stirringthe reaction mixture was stirred under ice-
  2. temperaturecooling for 1 hour
  3. stirringthe resulting solution was stirred under ice-
  4. temperaturecooling for 1 hour
  5. temperaturecooling
  6. stirringstirred for 30 minutes at the same temperature
  7. customThe aqueous layer was separated
  8. additionwas added to the aqueous layer
  9. stirringunder stirring
  10. customThe organic layer was separated
  11. washwashed with brine (20 ml)
  12. dry with materialdried over magnesium sulfate
  13. distillationThe solvent was distilled off
  14. filtrationcollected by filtration
  15. washwashed with IPE (20 ml)
  16. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-ec3cd8e5137f4939b98040fabbdad0df
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

Loading…