Pyridine → Benzhydryl 7-amino-3-acetyl-2-cephem-4-carboxylate

HRID 596838Notes

Reaction equation

HRID 596838 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.S1C=CC=C1CC([NH:15][CH:16]1[C:42](=[O:43])[N:18]2[CH:19]([C:26]([O:28][CH:29]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:27])[C:20]([C:23](=[O:25])[CH3:24])=[CH:21][S:22][C@H:17]12)=O.N1C=CC=CC=1.C(Cl)Cl>CCCCCC.C(O)C(C)C>[NH2:15][CH:16]1[C:42](=[O:43])[N:18]2[CH:19]([C:26]([O:28][CH:29]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:27])[C:20]([C:23](=[O:25])[CH3:24])=[CH:21][S:22][C@H:17]12

Participants

7

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 24819Phosphorus pentachlorideHCID 70636001Benzhydryl 7-(2-thienylacetamido)-3-acetyl-2-cephem-4-carboxylate

Product 1

HCID 131710673Benzhydryl 7-amino-3-acetyl-2-cephem-4-carboxylateYield 64%

Reagents, catalysts & solvents 2

HCID 6560IsobutanolSolventHCID 8058HexaneSolvent

Procedure

Phosphorous pentachloride (0.478 g.) was added to a stirred solution of 1.065 g. of benzhydryl 7-(2-thienylacetamido)-3-acetyl-2-cephem-4-carboxylate and 0.199 ml. of pyridine in 9 ml. of methylene chloride. The reaction mixture was allowed to stir at room temperature for 2.5 hours. After cooling the mixture for 5 minutes in an ice bath, 0.985 ml. of isobutanol was added, and the reaction mixture was subsequently stirred at room temperature for one hour. The addition of n-hexane resulted in the formation of a brown solid from which the liquid was decanted. The residue was dissolved in an ethyl acetate-aqueous sodium bicarbonate slurry and transferred to a separatory funnel with the aid of ethyl acetate. The organic layer was separated and washed successively with aqueous sodium bicarbonate solution, water, and brine (2X), and dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness provided a product which was chromatographed on a silica gel column using a toluene-ethyl acetate gradient to give a 0.521 g. (64 percent) of the title product as a tan froth:

Workup

  1. temperatureAfter cooling the mixture for 5 minutes in an ice bath
  2. stirringthe reaction mixture was subsequently stirred at room temperature for one hour
  3. customresulted in the formation of a brown solid from which the liquid
  4. customwas decanted
  5. dissolutionThe residue was dissolved in an ethyl acetate-aqueous sodium bicarbonate slurry
  6. customtransferred to a separatory funnel with the aid of ethyl acetate
  7. customThe organic layer was separated
  8. washwashed successively with aqueous sodium bicarbonate solution, water, and brine (2X)
  9. dry with materialdried over anhydrous sodium sulfate
  10. customEvaporation in vacuo to dryness
  11. customprovided a product which
  12. customwas chromatographed on a silica gel column
  13. customto give a 0.521 g

Sources & evidence

ORD record
ord-632e4774818046028ab902c67241b186
Source dataset
uspto-grants-1977_03
Patent number
US04012380

Reaction notes

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