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

HRID 2173968노트

반응식

HRID 2173968 반응식
[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

참가 물질

7

반응물 3

HCID 73974-Toluenesulfonyl chloride2회HCID 14798Sodium Hydroxide2회HCID 867015365-Chloro-7-methyl-4-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]-1H-indole

생성물 1

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

시약·촉매·용매 3

HCID 66133Benzyl triethylammonium chloride촉매HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-70de5831fe6f48f08c903f0e85766822
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056874B2

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