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

HRID 2173968Notes

Reaction equation

HRID 2173968 reaction equation
[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

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-70de5831fe6f48f08c903f0e85766822
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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