Acetonitrile → 6-fluoro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid

HRID 1054845노트

반응식

HRID 1054845 반응식
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])=[CH:15][CH:14]=1.C(#N)C.CC(=CC)C.Cl([O-])=[O:35].[Na+]>O.C(OCC)(=O)C.C(O)(C)(C)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:35])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])=[CH:17][CH:18]=1

참가 물질

8

반응물 4

HCID 6342AcetonitrileHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 866988376-fluoro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carbaldehyde

생성물 1

HCID 717660966-fluoro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid수율 40%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6386tert-Butanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

A round bottomed flask was charged with 6-fluoro-5-(2′-hydroxybiphenyl-4-yl)-1H-indole-3-carbaldehyde (20 mg, 0.60 mmol), acetonitrile, (1.0 mL), t-butanol (1.0 mL) and cooled to 0° C. 2-methyl-2-butene (0.49 mL, 4.6 mmol) was then added. In a separate flask, sodium chlorite (102 mg, 1.20 mmol) and NaH2PO4 (170 mg, 1.23 mmol) were dissolved in water (1 mL) then added to the reaction. The reaction was sealed and reacted at room temperature for 15 h. Ethyl acetate and water were added and the layers were separated. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Reverse phase HPLC was then used to provide the title compound (8.4 mg, 40%). MS (ES−) 346.1 (M−H)−. Retention time: 1.86 min Waters Xbridge dC18 5 um 4.6×50 mm, 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. (0.03% NH4OH). Flow: 2.0 mL/min.

후처리

  1. additionthen added to the reaction
  2. customThe reaction was sealed
  3. customreacted at room temperature for 15 h
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-b114122de4d949ef97073800c9e6cb98
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394285B2

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