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

HRID 2404489

반응식

HRID 2404489 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-13f43ecf969543ea9ebb2893940f9af8
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08802664B2

연결된 노트

불러오는 중…