Water → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(hydroxyiminomethyl)-benzamide

HRID 661718노트

반응식

HRID 661718 반응식
[Si]([O:8][CH2:9][CH2:10][O:11][NH:12][C:13](=[O:34])[C:14]1[CH:19]=[C:18]([CH:20]=[N:21][OH:22])[C:17]([F:23])=[C:16]([F:24])[C:15]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=1[F:33])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[F:24][C:16]1[C:15]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[C:14]([CH:19]=[C:18]([CH:20]=[N:21][OH:22])[C:17]=1[F:23])[C:13]([NH:12][O:11][CH2:10][CH2:9][OH:8])=[O:34]

참가 물질

5

반응물 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 74020017N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-(hydroxyiminomethyl)-benzamide

생성물 1

HCID 727586803,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(hydroxyiminomethyl)-benzamide수율 96%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-(hydroxyiminomethyl)-benzamide (a mixture of two geometric or atropisomers ) (5.0 mg, 46%) prepared in Process C was dissolved in THF (1 ml), tetrabutylammonium fluoride (1 M solution in THF, 30 μl, 30 μmol) was added thereto, and the mixture was stirred at room temperature for five hours. Water (8 ml) was added to the reaction solution, which was extracted with ethyl acetate (8 ml×3). The organic layers were combined, washed with 0.1 N hydrochloric acid (8 ml) and saturated brine (8 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with preparative thin layer chromatography (Silicagel 60 F254, 0.5 mm thickness, Merck & Co., Inc., CH2Cl2/MeOH (10:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(hydroxyiminomethyl)-benzamide (Compound 3) (3.9 mg, 96%) as a white solid.

후처리

  1. customatropisomers ) (5.0 mg, 46%) prepared in Process C
  2. extractionwas extracted with ethyl acetate (8 ml×3)
  3. washwashed with 0.1 N hydrochloric acid (8 ml) and saturated brine (8 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified with preparative thin layer chromatography (Silicagel 60 F254, 0.5 mm thickness, Merck & Co., Inc., CH2Cl2/MeOH (10:1))

출처 및 근거

ORD 기록
ord-4b2d091535f04aa3bcabaa63f233dafe
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084645B2

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