Pyridine → Benzhydryl 7-amino-3-cephem-4-carboxylate

HRID 1905808Notes

Reaction equation

HRID 1905808 reaction equation
[C:1]1([CH:7]([O:14][C:15]([CH:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH:25]C(=O)CC4C=CC=CC=4)[C@H:21]3[S:20][CH2:19][CH:18]2O)=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C(N(CC)CC)C>ClCCl.CO>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:35])[CH:24]([NH2:25])[C@H:21]3[S:20][CH2:19][CH:18]=2)=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 24819Phosphorus pentachlorideHCID 1364457351762-51-7

Product 1

HCID 12098365Benzhydryl 7-amino-3-cephem-4-carboxylateYield 47.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-hydroxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester (3e) in dichloromethane (13 parts) cooling at -5° to 0° C. under nitrogen are added at -5° to 0° C. pyridine (3 equivalents) and at -20° to -25° C. phosphorus pentachloride (2.7 equivalents). After stirring at -15° to -10° C. for 4 hours, the mixture is diluted with methanol (20 parts) cooled at -40° to -30° C. and stirred for 3 hours at -10° to -15° C. The mixture is cooled to -20° to -25° C., mixed dropwise with triethylamine (12 equivalents), and kept at 0° to 5° C. overnight. The mixture is diluted with ice-water (20 parts) and stirred at 0° to 5° C. for 20 minutes. The formed organic layer is washed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water, dried, and concentrated. The residue is crystallized from ethyl acetate to give 7beta-amino-3-cephem-4-carboxylic acid diphenylmethyl ester (5). Yield: 47.3%.

Workup

  1. temperaturecooling at -5° to 0° C. under nitrogen
  2. customat -20° to -25° C.
  3. temperaturecooled at -40° to -30° C.
  4. stirringstirred for 3 hours at -10° to -15° C
  5. temperatureThe mixture is cooled to -20° to -25° C.
  6. waitkept at 0° to 5° C. overnight
  7. stirringstirred at 0° to 5° C. for 20 minutes
  8. washThe formed organic layer is washed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water
  9. customdried
  10. concentrationconcentrated
  11. customThe residue is crystallized from ethyl acetate

Sources & evidence

ORD record
ord-2e7cd06de802473e8b6a501160907c18
Source dataset
uspto-grants-1987_03
Patent number
US04647658

Reaction notes

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