Pyridine → Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylate

HRID 1381394Notes

Reaction equation

HRID 1381394 reaction equation
P(Cl)(Cl)(Cl)(Cl)[Cl:2].N1C=CC=CC=1.C(NC(C(OC(C1C=CC=CC=1)C1C=CC=CC=1)=O)CCCC([NH:28][CH:29]1[C:54](=[O:55])[N:31]2[C:32]([C:38]([O:40][CH:41]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[O:39])=[C:33]([CH2:36]O)[CH2:34][S:35][C@H:30]12)=O)(=O)C1C=CC=CC=1.C(OC(C)C)(C)C>C(Cl)Cl.O.CO>[NH2:28][CH:29]1[C:54](=[O:55])[N:31]2[C:32]([C:38]([O:40][CH:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[O:39])=[C:33]([CH2:36][Cl:2])[CH2:34][S:35][C@H:30]12

Participants

8

Reactant 4

HCID 1049PyridineHCID 7914Diisopropyl EtherHCID 24819Phosphorus pentachlorideHCID 12817988HCID 12817988, compound

Product 1

HCID 13239626Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylateYield 26%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

To a suspension of phosphorus pentachloride (27.0 g) in methylene chloride (200 ml) was added dropwise pyridine (10.3 g) at 0° C., followed by stirring at 5° C. for 20 minutes. Thereto was added at a time benzhydryl 7-(5-benzamido-5-benzhydryloxycarbonylpentanamido)-3-hydroxymethyl-3-cephem-4-carboxylate (21.0 g) at -40° C., followed by stirring at -30° C. for an hour and at -10° C. for additional an hour. To the reaction mixture was added at a time at -40° C. methanol (100 ml), which was pre-cooled to -40° C., followed by stirring at -10° C. for an hour. Removal of the solvent gave a residue, to which methylene chloride (100 ml), water (30 ml) and diisopropyl ether (100 ml) were added in turn, and the mixture was stirred under ice-cooling for a while. The precipitated crystals were collected by filtration and suspended in ethyl acetate (300 ml), followed by adjusting to pH 8.0 with an aqueous sodium bicarbonate. The separated organic solution was washed with an aqueous sodium chloride and then dried over magnesium sulfate. Removal of the solvent gave benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (2.8 g), mp 135°-140° C. (dec.).

Workup

  1. stirringby stirring at -30° C. for an hour and at -10° C. for additional an hour
  2. temperaturewas pre-cooled to -40° C.
  3. stirringby stirring at -10° C. for an hour
  4. customRemoval of the solvent
  5. customgave a residue
  6. stirringthe mixture was stirred under ice-
  7. temperaturecooling for a while
  8. filtrationThe precipitated crystals were collected by filtration
  9. washThe separated organic solution was washed with an aqueous sodium chloride
  10. dry with materialdried over magnesium sulfate
  11. customRemoval of the solvent

Sources & evidence

ORD record
ord-bd8a275c558b4393a205823a7652557e
Source dataset
uspto-grants-1986_04
Patent number
US04585860

Reaction notes

Loading…