Glycerol → 6-Bromo-7-methoxyquinoline

HRID 579326

反応式

HRID 579326 の反応式
S(=O)(=O)(O)O.[N+]([C:9]1[CH:10]=C(S(O)(=O)=O)C=C[CH:14]=1)([O-])=O.OCC(CO)O.[Br:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][C:27]=1[O:33][CH3:34]>O>[Br:25][C:26]1[CH:32]=[C:31]2[C:29](=[CH:28][C:27]=1[O:33][CH3:34])[N:30]=[CH:10][CH:9]=[CH:14]2

参加物

6

反応物 4

HCID 753Glycerol2 回HCID 1118Sulfuric Acid2 回HCID 73873-Nitrobenzenesulfonic acidHCID 70182544-Bromo-3-methoxyaniline

生成物 1

HCID 867271476-Bromo-7-methoxyquinoline収率 51.3%

試薬・触媒・溶媒 1

HCID 962Water溶媒2 回

反応条件

温度
140 °C

実験手順

In a 100 mL round-bottom flask, a solution of concentrated sulfuric acid (2.1 mL, 39.6 mmol) in water (2.4 mL) was treated with 3-nitrobenzenesulfonic acid (2.06 g, 10.1 mmol) and glycerol (2.5 mL, 34.8 mmol) to give a thick grey suspension. The mixture was heated to 110° C. (oil bath) and 4-bromo-3-methoxyaniline (1.952 g, 9.66 mmol) was added portion-wise, resulting in an immobile slurry. Additional portions of water (3 mL), glycerol (3 mL), and concentrated sulfuric acid (3 mL) were added and the temperature increased to 140° C. After three hours the mixture had become a homogeneous dark brown solution, and LCMS analysis indicated reaction completion. The solution was cooled to RT, poured onto ice, and the pH was adjusted to 8 by addition of concentrated (30%) aqueous ammonium hydroxide. The mixture was partitioned between ethyl acetate and water, washed with water, brine, dried over magnesium sulfate and concentrated to a brown liquid. Purification by flash column chromatography (24 g silica gel, gradient of 0-20% ethyl acetate in dichloromethane over 25 column volumes) provided 6-bromo-7-methoxyquinoline (1.18 g, 46.2%) as a light brown fluffy solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 8.86 (dd, J=4.0, 1.5 Hz, 1H), 8.01-8.12 (m, 2H), 7.53 (s, 1H), 7.34 (dd, J=8.1, 4.5 Hz, 1H), 4.07 (s, 3H). NMR indicates the presence of about 10% 7-methyoxyquinoline. The mixture was taken on without further purification.

後処理

  1. customto give a thick grey suspension
  2. additionwas added portion-wise
  3. customresulting in an immobile slurry
  4. customreaction completion
  5. temperatureThe solution was cooled to RT
  6. additionpoured onto ice
  7. additionthe pH was adjusted to 8 by addition
  8. concentrationof concentrated (30%) aqueous ammonium hydroxide
  9. customThe mixture was partitioned between ethyl acetate and water
  10. washwashed with water, brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated to a brown liquid
  13. customPurification by flash column chromatography (24 g silica gel, gradient of 0-20% ethyl acetate in dichloromethane over 25 column volumes)

出典と根拠

ORDレコード
ord-fcda121506c14146878063cae5c3e36c
出典データセット
uspto-grants-2015_05
特許番号
US09040712B2

関連ノート

読み込み中…