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

HRID 1905804Notes

Reaction equation

HRID 1905804 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.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 137854823-Acetoxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester

Product 1

HCID 12098365Benzhydryl 7-amino-3-cephem-4-carboxylateYield 60.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-acetoxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester (3a) in dichloromethane (13 parts) under nitrogen are added at -5° to 0° C. pyridine (2 equivalents) and at -25° to -20° C. phosphorus pentachloride. After stirring at -15° to -10° C. for 4 hours, the mixture is diluted with a mixture of methanol (20 parts) and dichloromethane (5 parts) cooled at -40° to -30° C., and stirred at -30° to -25° C. for 3.5 hours. To the mixture keeping at -25° to -20° C. is dropwise added triethylamine (10.9 equivalents). After keeping at 0° to 5° C. overnight, the mixture is diluted with 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 7betaamino-3-cephem-4-carboxylic acid diphenylmethyl ester (5). Yield: 60.2%.

Workup

  1. customat -25° to -20° C.
  2. temperaturecooled at -40° to -30° C.
  3. stirringstirred at -30° to -25° C. for 3.5 hours
  4. customkeeping at -25° to -20° C.
  5. waitAfter keeping at 0° to 5° C. overnight
  6. stirringstirred for 20 minutes
  7. washwashed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water
  8. customdried
  9. concentrationconcentrated
  10. customThe residue is crystallized from ethyl acetate

Sources & evidence

ORD record
ord-ca33f13974f24636a8a936139d479f60
Source dataset
uspto-grants-1987_03
Patent number
US04647658

Reaction notes

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