4-Toluenesulfonyl chloride → 5-Bromo-1-(4-methylbenzene-1-sulfonyl)-1H-indole

HRID 2253550Notes

Reaction equation

HRID 2253550 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[OH-].[K+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:17]([C:14]1[CH:15]=[CH:16][C:11]([CH3:21])=[CH:12][CH:13]=1)(=[O:19])=[O:18])[CH:6]=[CH:5]2

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 14797Potassium HydroxideHCID 249055-Bromoindole

Product 1

HCID 119546185-Bromo-1-(4-methylbenzene-1-sulfonyl)-1H-indoleYield 99.9%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Procedure

A 100 mL round bottom flask was sequentially charged with 5-bromoindole (1.96 g, 10 mmol), p-toluenesulfonyl chloride (2.30 g, 12 mmol), tetrabutylammonium hydrogen sulfate (240 mg, 0.70 mmol) and toluene (40 mL). An aqueous solution of potassium hydroxide (13 mL, 50%) was added dropwise and the mixture was stirred at room temperature overnight. At this point the organic layer was separated, diluted with ethyl ether (40 mL), washed with two portions of dilute potassium hydroxide solution (2×20 mL, 2M) and dried over MgSO4. The solvent was removed at reduced pressure and the product was purified by flash chromatography on silica gel (hexane/ethyl acetate 1:1) to provide the desired product as a light yellow solid (3.50 g,99% yield). Mp 135° C. (lit. 139-140° C., See Fresneda, M. P.; Molina, P.; Bleda, A. J. Tetrahedron 2001, 57, 2355). 1H NMR (400 MHz, CDCl3, J values are reported in Hz, lit. See Fresneda, M. P.; Molina, P.; Bleda, A. J. Tetrahedron 2001, 57, 2355): δ 7.88 (d, J=8.8, 1H), 7.76 (d, J=8.6, 2H), 7.68 (d, J=1.8, 1H), 7.59 (d, J=3.5, 1H), 7.42 (dd, J=8.8, J=2.0, 1H), 7.25 (d, J=8.6, 2H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 145.7, 135.3, 133.9, 132.9, 130.4, 128.0, 127.9, 127.2, 124.5, 117.2, 115.4, 108.7, 22.0.

Workup

  1. customAt this point the organic layer was separated
  2. additiondiluted with ethyl ether (40 mL)
  3. washwashed with two portions of dilute potassium hydroxide solution (2×20 mL, 2M)
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed at reduced pressure
  6. customthe product was purified by flash chromatography on silica gel (hexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-41a59dd559714dd89dfa25993bfe82dd
Source dataset
uspto-grants-2008_01
Patent number
US07323608B2

Reaction notes

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