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

HRID 36300

反応式

HRID 36300 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][C:19]=2[F:38])[C:13]([CH2:39][CH2:40][CH2:41][CH3:42])=[N:12]1.Cl[C:44]([F:50])([F:49])C(OC)=O.[F-:51].[K+].[Br-].[K+]>O.CN(C=O)C>[CH2:39]([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]([CH3:35])([CH3:34])[CH3:33])=[CH:20][C:19]=2[F:38])[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:44]([F:50])([F:51])[F:49])[N:12]=1)[CH2:40][CH2:41][CH3:42]

参加物

7

反応物 4

HCID 73935Methyl chlorodifluoroacetateHCID 253877Potassium BromideHCID 522689Potassium FluorideHCID 103494052-(2-Bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one

生成物 1

HCID 117648385-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-2,4-dihydro-2-[5-nitro-2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one収率 62%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 400 mg (0.606 mmol) of 2-(2-bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step C), 128 μL (175 mg (1.21 mmol) of methyl chlorodifluoroacetate. 42 mg (0.73 mmol) of potassium fluoride, 116 mg (0.606 mmol) of cuprous iodide, 72 mg (0.606 mmol) of potassium bromide, and 1.2 mL of DMF was stirred under N2 at 120° C. in a sealed tube for 15 hours. The cooled mixture was diluted with water and extracted 3× with ethyl acetate. The combined organic fractions were washed with brine, dried (Na2SO4), and filtered. The filtrate was concentrated, and the residue was flash chromatographed on silica gel (elution with 6:1 hexane-EtOAc) to give 243 mg (62%) of the title compound as a pale yellow foam. [Subsequently eluted was 28 mg of the 2-chloro-5-nitrophenyl analog.] The desired product was homogeneous by TLC in 5:1 hexane-EtOAc; mass spectrum (FAB) m/e 656 (M+Li)+.

後処理

  1. extractionextracted 3× with ethyl acetate
  2. washThe combined organic fractions were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customchromatographed on silica gel (elution with 6:1 hexane-EtOAc)

出典と根拠

ORDレコード
ord-78a73e2c2c6140ddb16318afc77ad277
出典データセット
uspto-grants-1995_05
特許番号
US05411980

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