2-Methylpyridine → 6-bromo-3-(1-hydroxy-2-pyridin-2-ylethyl)-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one

HRID 750359ノート

反応式

HRID 750359 の反応式
C([Li])CCC.[CH3:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[Br-].[Mg+2].[Br-].[Br:16][Mg:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[Br:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[N:31]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1)[C:30]([CH:48]=[O:49])=[C:29]2[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.C(=O)([O-])O.[Na+]>CCCCCC.C1COCC1.O>[Br:16][Mg:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[Br:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[N:31]([CH2:37][C:38]1[CH:39]=[CH:40][C:41]([S:44]([CH3:47])(=[O:45])=[O:46])=[CH:42][CH:43]=1)[C:30]([CH:48]([OH:49])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)=[C:29]2[C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1

参加物

11

反応物 6

HCID 79752-MethylpyridineHCID 82241Magnesium BromideHCID 516892Sodium BicarbonateHCID 230608166-Bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehydeHCID 178418339ButyllithiumHCID 178419667HCID 178419667、化合物

生成物 2

HCID 230609606-bromo-3-(1-hydroxy-2-pyridin-2-ylethyl)-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-oneHCID 178419667HCID 178419667、化合物

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回HCID 8058Hexane溶媒

反応条件

温度
-20 °C

実験手順

Under a nitrogen stream, a solution (1.61M, 15.8 ml) of n-butyllithium in hexane was added to THF (15 ml) at −50° C. or below, and a solution (2.5 ml) of 2-methylpyridine (2.5 g) in THF was added dropwise at −50° C. or below. The reaction mixture was allowed to warm to −20° C. and stirred for 10 min. and then cooled to −50° C. and magnesium bromide (2.5 g) was added. The reaction mixture was allowed to warm to room temperature, stirred for 30 min. and bromo(pyridin-2-ylmethyl)magnesium was prepared. The obtained suspension (4 ml) of bromo(pyridin-2-ylmethyl)magnesium was added to a solution of 6-bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehyde (500 mg) in THF (5 ml), and the mixture was stirred at room temperature for 10 min. To the reaction mixture were added water and saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (ethyl acetate) to give the title compound (400 mg).

後処理

  1. temperaturecooled to −50° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 30 min.
  4. stirringthe mixture was stirred at room temperature for 10 min
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate)

出典と根拠

ORDレコード
ord-6e30e1853e6043458b744c32723f3cc7
出典データセット
uspto-grants-2008_07
特許番号
US07402595B2

反応ノート

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