2,4-Difluoroanisole → (2,6-difluoro-3-methoxyphenyl)[1-(2-trimethylsilylethoxymethyl)-1H-benzimidazol-2-yl]methanol

HRID 2404489

反応式

HRID 2404489 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][CH3:10].C([N-]C(C)C)(C)C.[Li+].[CH3:19][Si:20]([CH3:37])([CH3:36])[CH2:21][CH2:22][O:23][CH2:24][N:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1[CH:34]=[O:35]>O1CCCC1>[F:1][C:2]1[C:3]([O:9][CH3:10])=[CH:4][CH:5]=[C:6]([F:8])[C:7]=1[CH:34]([C:26]1[N:25]([CH2:24][O:23][CH2:22][CH2:21][Si:20]([CH3:36])([CH3:37])[CH3:19])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=1)[OH:35]

参加物

5

反応物 3

HCID 1362932,4-DifluoroanisoleHCID 2724682Lithium diisopropylamideHCID 120171281-(2-Trimethylsilylethoxymethyl)-2-formyl-benzimidazole

生成物 1

HCID 66836061(2,6-difluoro-3-methoxyphenyl)[1-(2-trimethylsilylethoxymethyl)-1H-benzimidazol-2-yl]methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

To a solution of 2,4-difluoro-1-methoxybenzene (156 mg) in tetrahydrofuran (5 mL) at −78° C. is added a 2M solution of lithium diisopropylamide in THF (540 μL). After stirring for 45 min a solution of 1-(2-trimethylsilylethoxymethyl)-1H-benzimidazole-2-carbaldehyde (which can be prepared according to US2003/220341 or U.S. Pat. No. 6,476,041 for example) (300 mg) in tetrahydrofuran (5 mL) is added at −78° C. and the reaction mixture allowed to warm to room temperature. After hydrolysis with aqueous saturated ammonium chloride and extraction with ethyl acetate, the organic phase is dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 95/5) to afford (2,6-difluoro-3-methoxyphenyl)[1-(2-trimethylsilylethoxymethyl)-1H-benzimidazol-2-yl]methanol.

後処理

  1. customcan be prepared
  2. customis added at −78° C.
  3. customAfter hydrolysis
  4. extractionwith aqueous saturated ammonium chloride and extraction with ethyl acetate
  5. dry with materialthe organic phase is dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 95/5)

出典と根拠

ORDレコード
ord-13f43ecf969543ea9ebb2893940f9af8
出典データセット
uspto-grants-2014_08
特許番号
US08802664B2

関連ノート

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