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

HRID 1905809Notes

Reaction equation

HRID 1905809 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.C(O)C(C)C>[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 37.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6560IsobutanolSolvent

Procedure

To a suspension of the said starting material (3e) in dichloromethane (13 parts) under nitrogen are added at -5° to 0° C. pyridine (3 equivalents) and at -25° to -20° C. phosphorus pentachloride (2.7 equivalents). After stirring at -15° to -10° C. for 4 hours, the mixture is mixed with isobutanol (11 parts) cooled at -40° to -30° C., stirred at 0° to 5° C. for 2 hours, and kept at 0° to 5° C. overnight. The mixture is cooled to -25° to -20° C., mixed dropwise with triethylamine (14 equivalents), and kept at 0° to 5° C. overnight. The mixture is diluted with a mixture of ice-water and dichloromethane, and stirred for 20 minutes. The formed organic layer is taken, 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: 37.2%.

Workup

  1. customat -25° to -20° C.
  2. temperaturecooled at -40° to -30° C.
  3. stirringstirred at 0° to 5° C. for 2 hours
  4. waitkept at 0° to 5° C. overnight
  5. temperatureThe mixture is cooled to -25° to -20° C.
  6. waitkept at 0° to 5° C. overnight
  7. stirringstirred for 20 minutes
  8. washwashed 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-d430c2c47a5a49be81bbb583109e70b9
Source dataset
uspto-grants-1987_03
Patent number
US04647658

Reaction notes

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