Lithium Hydroxide → 1-(3-Chlorobenzyl)-4-oxo-4,5,6,7-tetrahydroindole

HRID 2187113Notes

Reaction equation

HRID 2187113 reaction equation
[NH:1]1[C:9]2[CH2:8][CH2:7][CH2:6][C:5](=[O:10])[C:4]=2[CH:3]=[CH:2]1.[Cl:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15]Br.N1C=CC=C1.[H-].[Na+].C1(S(OC)=O)C=CC=CC=1.[OH-].[Li+]>O1CCCC1.O1CCOCC1.O.CCCCCC.C(OCC)(=O)C>[Cl:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15][N:1]1[C:9]2[CH2:8][CH2:7][CH2:6][C:5](=[O:10])[C:4]=2[CH:3]=[CH:2]1

Participants

12

Reactant 6

HCID 3939Lithium HydroxideHCID 8027PyrroleHCID 24758Sodium hydrideHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 2802291,5,6,7-Tetrahydro-4H-indol-4-oneHCID 2759784Methyl benzenesulfinate

Product 1

HCID 224506211-(3-Chlorobenzyl)-4-oxo-4,5,6,7-tetrahydroindole

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(3-chlorobenzyl)-4-oxo-4,5,6,7-tetrahydroindole was prepared from 1,5,6,7-tetrahydro-4H-indol-4-one and 3-chlorobenzylbromide using methodology common to the art. The pyrrole (0.5 g, 1.9 mmol) was dissolved in tetrahydrofuran (2.5 mL). Sodium hydride (0.18 g, 4.4 mmol) was added. After 5 minutes, methyl benzenesulfinate (0.48 g, 3.1 mmol) was added. The color of the mixture darkened to red as gas evolution was observed. The mixture was stirred for 1 hour. Thin layer chromatography indicated complete consumption of starting material (sulfoxides, Rf 0.11; 1/1 hexane/ethyl acetate). The reaction mixture was quenched with water, stirred for 10 minutes, and diluted with chloroform. The solution was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and evaporated to give an orange oil. The oil was dissolved in dioxane (5 mL) and refluxed for 3 hours at which time the sulfoxides were no longer observed by thin layer chromatography. The reaction mixture was cooled to room temperature and a solution of lithium hydroxide (85 mg) in water (2 mL) was added. The solvent was evaporated and the residue was dissolved in chloroform. The solution was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and evaporated to give an orange oil. Column chromatography with 20% ethyl acetate in hexane provided 0.41 g of a yellow solid. (81% yield) TLC Rf 0.28 (20% EtOAc in hexane); 1H NMR (CDCl3): d 7.30 (d, J=8.2, 1 H), 7.24 (t, J=7.8, 1 H), 7.18 (s, 1 H), 7.11 (t, J=7.9, 1 H), 7.07 (d, J=3.2, 1 H), 6.98 (d, J=7.6, 1 H), 6.92 (d, J=8.3, 1 H), 6.75 (d, J=3.3, 1 H), 6.63 (d, J=7.6, 1 H), 6.01 (s, 1 H), 5.24 (s, 2 H).

Workup

  1. customconsumption of starting material (sulfoxides, Rf 0.11; 1/1 hexane/ethyl acetate)
  2. customThe reaction mixture was quenched with water
  3. stirringstirred for 10 minutes
  4. additiondiluted with chloroform
  5. washThe solution was washed with saturated sodium bicarbonate solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto give an orange oil
  9. customThe solvent was evaporated
  10. dissolutionthe residue was dissolved in chloroform
  11. washThe solution was washed with saturated sodium bicarbonate solution
  12. dry with materialdried over anhydrous sodium sulfate
  13. customevaporated
  14. customto give an orange oil

Sources & evidence

ORD record
ord-c1df6fe82c684d04a0c2644a26dca528
Source dataset
uspto-grants-2002_06
Patent number
US06407261B1

Reaction notes

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