Sodium hydride → (2-Bromophenyl)(difluoro)methyl 4'-(trifluoromethyl)biphenyl-4-yl ether 4-[(2-bromophenyl)(difluoro)methoxy]-4'-(trifluoromethyl)biphenyl

HRID 1255226ノート

反応式

HRID 1255226 の反応式
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[H-].[Na+].[H][H].[Br:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29](Br)([F:31])[F:30]>CN(C=O)C>[F:1][C:2]([F:16])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:29]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[Br:22])([F:31])[F:30])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[Br:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]([F:31])([F:30])[O:15][C:12]1[CH:13]=[CH:14][C:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:16])([F:17])[F:1])=[CH:4][CH:5]=2)=[CH:10][CH:11]=1

参加物

6

反応物 4

HCID 24758Sodium hydrideHCID 155411804-(4-Trifluoromethylphenyl)phenolHCID 671595551-Bromo-2-[bromo(difluoro)methyl]benzeneHCID 178418361HCID 178418361、化合物

生成物 1

HCID 86633503(2-Bromophenyl)(difluoro)methyl 4'-(trifluoromethyl)biphenyl-4-yl ether 4-[(2-bromophenyl)(difluoro)methoxy]-4'-(trifluoromethyl)biphenyl

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a cooled (0° C.) solution of 4′-(trifluoromethyl)[1,1′-biphenyl]-4-ol (178 mg, 0.75 mmol) in DMF was added sodium hydride (27.0 mg, 1.12 mmol). Once the hydrogen evolution subsided, the reaction mixture was allowed to warm to ambient temperature. The title compound from Example 303 Step A (373 mg, 1.30 mmol) was then added to the reaction flask, and the reaction mixture was stirred at 60° C. After 15 h, the reaction mixture was quenched by addition of 2 N aqueous HCl. The aqueous phase was extracted with hexanes/ethyl acetate (3:1 v/v). The organic phase was separated, dried over sodium sulfate and concentrated in vacuo. Purification was by flash chromatography on silica gel (0-20% dichloromethane in hexanes) provided the title compound: LCMS m/z 423.5 [M−F]+; 1H NMR (500 MHz, CD2Cl2) δ 7.85 (dd, J=7.8, 1.6 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.72 (s, 4H), 7.65 (dd, J=6.8, 1.9 Hz, 2H), 7.45 (d, J=8.7 Hz, 3H), 7.40 (td, J=7.7, 1.5 Hz, 1H).

後処理

  1. customthe reaction mixture was quenched by addition of 2 N aqueous HCl
  2. extractionThe aqueous phase was extracted with hexanes/ethyl acetate (3:1 v/v)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification

出典と根拠

ORDレコード
ord-77363fcdcc7c45958d9abafda5995372
出典データセット
uspto-grants-2013_06
特許番号
US08455638B2

反応ノート

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