Methyl iodide → 1-Methyl-2-phenylindole

HRID 48901

Reaction equation

HRID 48901 reaction equation
[CH2:1]1COCC1.[C:6]1([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[H-].[Na+].CI>O>[CH3:1][N:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:20]=[C:12]1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 136982-PhenylindoleHCID 24758Sodium hydride

Product 1

HCID 770951-Methyl-2-phenylindoleYield 79%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

A solution of dry THF containing 2-phenylindole (1 mmole) was added NaH (1.1 mmole) and MeI (1.2 mmole, dropwise), and the reaction mixture was stirred at 65° C. for 3 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with ether. The extracts was dried (MgSO4) and evaporated under reduced pressure to give yellow-orange solid. Further purification by column chromatography on silica gel with hexane as an eluent gave a pale yellow solid of 1-methyl-2-phenylindole (79% yield). The solid product (0.7 mmole) was dissolved in DMF (10 ml), a mixture of POCl3(0.09 mmole) and DMF (0.09 mmole) was added dropwise. After stirring at 75° C. for 1 h, the reaction mixture was added into saturate NaHCO3solution. The precipitated solid was collected by filtration and washed with ethanol to give a pale gray solid of 1-methyl-2-phenylindole-3-carboxaldehyde (85% yield). A dry DMF solution of the aldehyde (2 mmole) was added o-aminothiophenol (2.1 mmole) and Ac2O (0.5 ml) at room temperature. The mixture was stirred at 60° C. for 3 h. The reaction mixture was poured into stirred water and the precipitated solid was collected by filtration. The crude solid was washed with MeOH and recrystallized from benzene to afford compound 1-2 (38% yield). 1H-NMR (CDCl3, TMS) δ(ppm)=3.6 (s, 3H, —CH3), 7.3-7.8, 8.1, 8.9 (m, d, m, 13H, aromatic H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ether
  3. dry with materialThe extracts was dried (MgSO4)
  4. customevaporated under reduced pressure
  5. customto give yellow-orange solid
  6. customFurther purification by column chromatography on silica gel with hexane as an eluent

Sources & evidence

ORD record
ord-b45e070aca2446ab930ae18eee1dbc16
Source dataset
uspto-grants-2004_03
Patent number
US06706423B2

Linked notes

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