Phenethyl tosylate → 1-phenethyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indole

HRID 1766239Notes

Reaction equation

HRID 1766239 reaction equation
[Si]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)(C(C)(C)C)(C)C.[H-].[K+].S(C1C=CC(C)=CC=1)(O[CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=O)=O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH2:31]([N:14]1[C:15]2[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=2)[C:12]([CH:18]2[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]2)=[CH:13]1)[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 20522Phenethyl tosylateHCID 82127Potassium hydride2×HCID 2724141Tetrabutylammonium FluorideHCID 179801335-(t-Butyldimethylsilanyloxy)-3-(1-methylpiperidin-4-yl)-1H-indol

Product 1

HCID 179801211-phenethyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indoleYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To solution of 5-(t-butyldimethylsilanyloxy)-3-(1-methylpiperidin-4-yl)-1H-indol (285 mg, 0.83 mmol) in tetrahydrofuran (20 mL) stirring at 0° C. was treated with potassium hydride (99 mg of a 35% dispersion in oil, 0.87 mmol). The light yellow solution was stirred for 20 minutes at 0° C. Phenethyl tosylate (2.29 g, 8.30 mmol) was added and stirred at 0° C. for 3 h, and at room temperature overnight. Addition 35% potassium hydride (94 mg, 0.83 mmol) was added and the reaction was stirred at room temperature overnight. The mixture was treated with tetrabutylammonium fluoride (830 μL of a 1M solution in tetrahydrofuran, 0.83 mmol) and was stirred overnight at room temperature, before concentrating in vacuo. Purification by silica gel chromatography 9:1 dichloromethane: methanol gave 175 mg (63%) of the title compound as orange foam: MS (APCI): m/e 335.2 (M+1).

Workup

  1. stirringstirred at 0° C. for 3 h
  2. customat room temperature
  3. customovernight
  4. additionwas added
  5. stirringthe reaction was stirred at room temperature overnight
  6. stirringwas stirred overnight at room temperature
  7. concentrationbefore concentrating in vacuo
  8. customPurification by silica gel chromatography 9:1 dichloromethane

Sources & evidence

ORD record
ord-05ce864a61d645a2b912a3f02d27210e
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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