تفاعل #51132

ord-a0d0a57b98aa4ae98b108254648bbe0c

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىsolvent removed by evaporation under diminished pressure
  2. 2
    workup.DISSOLUTIONThe residue was redissolved in anhydrous toluene (2 mL)
  3. 3
    درجة الحرارةThe mixture was refluxed for 18 h
  4. 4
    درجة الحرارةThe reaction was cooled to room temperature
  5. 5
    ترشيحthe cream-colored precipitate was filtered
  6. 6
    غسيلwashed
  7. 7
    أخرىto give 300 mg of crude product as the HCl salt
  8. 8
    غسيلthe aqueous layer was washed with two additional portions of methylene chloride
  9. 9
    أخرىevaporated
  10. 10
    أخرىthe residue was chromatographed by flash silica gel chromatography
  11. 11
    غسيلElution
  12. 12
    أخرىevaporated

الإجراء التجريبي

Methyl amide 10-5 (220 mg, 0.77 mmol) was dissolved in anhydrous methylene chloride (2 mL) and treated with oxalyl chloride (2M in methylene chloride, 0.77 mL, 1.54 mmol) and DMF (2 drops). The solution was stirred at room temperature for 1 h, then solvent removed by evaporation under diminished pressure. The residue was redissolved in anhydrous toluene (2 mL) and treated with 5[2-(trifluoromethyl)phenyl]1H-tetrazole (214 mg, 1 mmol). The mixture was refluxed for 18 h. The reaction was cooled to room temperature and the cream-colored precipitate was filtered and washed to give 300 mg of crude product as the HCl salt. The salt was taken up in methylene chloride/1N HCl and the aqueous layer was washed with two additional portions of methylene chloride. The organic layers were combined and evaporated and the residue was chromatographed by flash silica gel chromatography. Elution was carried out with a gradient ranging from 0 to 5% methanol/methylene chloride. The appropriate fractions were combined and evaporated to give 3-{4-[2-(ethylsulfonyl)ethyl]bicyclo[2.2.2]oct-1-yl}-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H -1,2,4-triazole (10-6) as a white powder.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US06849636B2uspto-grants-2005_02