Methyl chlorodifluoroacetate → 5-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-2,4-dihydro-2-[5-nitro-2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

HRID 36278

反応式

HRID 36278 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[S:30](=[O:37])(=[O:36])[NH:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:20][CH:19]=2)[C:13]([CH2:38][CH2:39][CH2:40][CH3:41])=[N:12]1.[F-:42].[K+].Cl[C:45]([F:51])([F:50])C(OC)=O>CN(C=O)C.O>[CH2:38]([C:13]1[N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[S:30](=[O:36])(=[O:37])[NH:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:20][CH:19]=2)[C:15](=[O:16])[N:11]([C:3]2[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=2[C:45]([F:51])([F:42])[F:50])[N:12]=1)[CH2:39][CH2:40][CH3:41]

参加物

6

反応物 3

HCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 100779172-(2-Bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one

生成物 1

HCID 103942615-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-2,4-dihydro-2-[5-nitro-2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one収率 37%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

To a solution of 600 mg (0.935 mmol) of 2-(2-bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step B) in 1.87 mL of DMF were added 65 mg (1.12 mmol) of potassium fluoride, 179 mg (0.935 mmol) of cuprous iodide, and 197 μL (270 mg, 1.87 mmol) of methyl chlorodifluoroacetate. The mixture was stirred in a sealed tube at 120° C. for 12 hours. The cooled mixture was diluted with H2O and extracted 3× with ethyl acetate. The combined organic extracts were washed with H2O, then brine, and dried over Na2SO4. The residue obtained upon evaporation of the filtered solution was flash chromatographed on silica gel (gradient elution with 8.5:1 to 5:1 hexane-EtOAc) to give 216 mg (37%) of the title compound as a solid, mp 135°-137° C. [Subsequently eluted was 187 mg (32%) of the corresponding 2-chloro-5-nitrophenyl analog, obtained as a byproduct.] The desired product was homogeneous by TLC (98:2 CH2Cl2 --MeOH); mass spectrum (FAB) m/e 638 (M+Li)+ .

後処理

  1. extractionextracted 3× with ethyl acetate
  2. washThe combined organic extracts were washed with H2O
  3. dry with materialbrine, and dried over Na2SO4
  4. customThe residue obtained upon evaporation of the filtered solution
  5. customchromatographed on silica gel (gradient elution with 8.5:1 to 5:1 hexane-EtOAc)

出典と根拠

ORDレコード
ord-d8dbdabd7d4e4c4888a02bd7c6497caa
出典データセット
uspto-grants-1995_05
特許番号
US05411980

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