Oxalyl chloride → 3-{4-[2-(Ethylsulfonyl)ethyl]bicyclo[2.2.2]oct-1-yl}-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole

HRID 22854노트

반응식

HRID 22854 반응식
[CH2:1]([S:3]([CH2:6][CH2:7][C:8]12[CH2:15][CH2:14][C:11]([C:16]([NH:18][CH3:19])=O)([CH2:12][CH2:13]1)[CH2:10][CH2:9]2)(=[O:5])=[O:4])[CH3:2].C(Cl)(=O)C(Cl)=O.[F:26][C:27]([F:40])([F:39])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]1NN=[N:36][N:35]=1>C(Cl)Cl.CN(C=O)C>[CH2:1]([S:3]([CH2:6][CH2:7][C:8]12[CH2:15][CH2:14][C:11]([C:16]3[N:18]([CH3:19])[C:34]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=4[C:27]([F:26])([F:40])[F:39])=[N:35][N:36]=3)([CH2:12][CH2:13]1)[CH2:10][CH2:9]2)(=[O:5])=[O:4])[CH3:2]

참가 물질

6

반응물 3

HCID 65578Oxalyl chlorideHCID 207550374-[2-(ethylsulfonyl)ethyl]-N-methylbicyclo[2.2.2]octane-1-carboxamideHCID 178506136HCID 178506136, 화합물

생성물 1

HCID 225917093-{4-[2-(Ethylsulfonyl)ethyl]bicyclo[2.2.2]oct-1-yl}-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  1. customsolvent removed by evaporation under diminished pressure
  2. dissolutionThe residue was redissolved in anhydrous toluene (2 mL)
  3. temperatureThe mixture was refluxed for 18 h
  4. temperatureThe reaction was cooled to room temperature
  5. filtrationthe cream-colored precipitate was filtered
  6. washwashed
  7. customto give 300 mg of crude product as the HCl salt
  8. washthe aqueous layer was washed with two additional portions of methylene chloride
  9. customevaporated
  10. customthe residue was chromatographed by flash silica gel chromatography
  11. washElution
  12. customevaporated

출처 및 근거

ORD 기록
ord-a0d0a57b98aa4ae98b108254648bbe0c
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06849636B2

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