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

HRID 1905805Notes

Reaction equation

HRID 1905805 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]2OC(=O)C)=[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 137854823-Acetoxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester

Product 1

HCID 12098365Benzhydryl 7-amino-3-cephem-4-carboxylateYield 60.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6560IsobutanolSolvent

Procedure

To a solution of the above starting material (3a) in dichloromethane (13 parts) under nitrogen are added at -5° to 0° C. pyridine (2 equivalents) and at -30° to -25° C. phosphorus pentachloride (1.7 equivalents). The mixture is stirred at -15° to -10° C. for 4 hours, cooled to -25° to -30° C., mixed with isobutanol (10 parts) cooled at -30° to -20° C., and let stand at 0° to 5° C. overnight. The reaction mixture is cooled to -20° to -25° C., mixed dropwise with triethylamine (10.9 equivalents), and kept at 0° to 5° C. overnight. The reaction mixture is diluted with dichloromethane (20 parts) and ice water (20 parts) 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: 60.8%.

Workup

  1. customat -30° to -25° C.
  2. temperaturecooled to -25° to -30° C.
  3. temperaturecooled at -30° to -20° C.
  4. waitlet stand at 0° to 5° C. overnight
  5. temperatureThe reaction mixture is cooled to -20° to -25° 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-2d708f4cb9db412e9e4c4a63bc6cbfdf
Source dataset
uspto-grants-1987_03
Patent number
US04647658

Reaction notes

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