4-Toluenesulfonyl chloride → 5-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole

HRID 2173968ノート

反応式

HRID 2173968 の反応式
[Cl:1][C:2]1[C:3]([CH2:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[NH:7][CH:6]=[CH:5]2.[OH-].[Na+].[S:22](Cl)([C:25]1[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23]>C(Cl)Cl.[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.O>[Cl:1][C:2]1[C:3]([CH2:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[N:7]([S:22]([C:25]1[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[CH:6]=[CH:5]2

参加物

7

反応物 3

HCID 73974-Toluenesulfonyl chloride2 回HCID 14798Sodium Hydroxide2 回HCID 867015365-Chloro-7-methyl-4-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]-1H-indole

生成物 1

HCID 867015385-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole

試薬・触媒・溶媒 3

HCID 66133Benzyl triethylammonium chloride触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (±)-5-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-indole (8.95 g, 32 mmol) in CH2Cl2 (150 mL), at 0° C. was added NaOH (2.56 g, 64.0 mmol), followed by triethylbenzylammonium chloride (0.729 g, 3.20 mmol) and TsCl (12.20 g, 64.0 mmol). The mixture was then stirred at room temperature. After 17 h, additional NaOH (1.28 g, 32.0 mmol), and TsCl (6.10 g, 32.0 mmol) were added. The mixture was stirred at room temperature for 1.5 h. The reaction mixture was diluted with H2O, and was vigorously stirred for 1 h. The mixture was diluted with CH2Cl2 and the organic layer was successively washed with H2O and brine, dried over Na2SO4, and then filtered. Concentration of the filtrate gave the crude product, which was purified by FCC [heptane/(30% EtOAc in CH2Cl2)=82/18 then 79/21] to give the title compound. 1H NMR (400 MHz, ACETONITRILE-d3) δ 7.84 (d, J=3.79 Hz, 1H), 7.67 (d, J=8.20 Hz, 1H), 7.59 (d, J=8.59 Hz, 1H), 7.48 (d, J=8.20 Hz, 1H), 7.33 (d, J=8.50 Hz, 1H), 7.13 (s, 1H), 6.97 (d, J=3.79 Hz, 1H), 4.97 (d, J=11.37 Hz, 1H), 4.76 (d, J=11.37 Hz, 1H), 4.61-4.70 (m, 1H), 3.79-3.91 (m, 1H), 3.40-3.52 (m, 1H), 2.53 (s, 3H), 2.36 (s, 3H), 1.58-1.75 (m, 2H), 1.38-1.58 (m, 4H).

後処理

  1. stirringThe mixture was stirred at room temperature for 1.5 h
  2. stirringwas vigorously stirred for 1 h
  3. washthe organic layer was successively washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customConcentration of the filtrate gave the crude product, which
  7. customwas purified by FCC [heptane/(30% EtOAc in CH2Cl2)=82/18

出典と根拠

ORDレコード
ord-70de5831fe6f48f08c903f0e85766822
出典データセット
uspto-grants-2015_06
特許番号
US09056874B2

反応ノート

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