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

HRID 1054845ノート

反応式

HRID 1054845 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 6386tert-Butanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-b114122de4d949ef97073800c9e6cb98
出典データセット
uspto-grants-2016_07
特許番号
US09394285B2

反応ノート

読み込み中…