Methyl iodide → 2-Methyl-1-[(1R)-1-methyl-2-(methyloxy)ethyl]-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 913740Notes

Reaction equation

HRID 913740 reaction equation
[OH:1][CH2:2][C@H:3]([N:5]1[C:13]2[C:8](=[C:9]([C:16]([F:19])([F:18])[F:17])[C:10]([C:14]#[N:15])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:20])[CH3:4].[H-].[Na+].I[CH3:24]>C1COCC1>[CH3:20][C:6]1[N:5]([C@H:3]([CH3:4])[CH2:2][O:1][CH3:24])[C:13]2[C:8]([CH:7]=1)=[C:9]([C:16]([F:19])([F:17])[F:18])[C:10]([C:14]#[N:15])=[CH:11][CH:12]=2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 674048201-[(1R)-2-Hydroxy-1-methylethyl]-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 674061702-Methyl-1-[(1R)-1-methyl-2-(methyloxy)ethyl]-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[(1R)-2-hydroxy-1-methylethyl]-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 329) (0.035 g, 0.124 mmol) in dry THF (5 mL) was added sodium hydride (60%, 0.0075 g, 0.188 mmol) at 0° C. The mixture was stirred at rt for 0.5 h and then was added iodomethane (77 uL, 1.24 mmol). The mixture was stirred at 50° C. in a sealed tube overnight. The resulting solids were filtered and the filtrate was then concentrated in vacuo. The residue was purified by radial chromatography (0-60% EtOAc-hexanes gradient) to afford the title compound (0.015 g, 41% yield): MS (ES) m/z 297 (M+1).

Workup

  1. stirringThe mixture was stirred at 50° C. in a sealed tube overnight
  2. filtrationThe resulting solids were filtered
  3. concentrationthe filtrate was then concentrated in vacuo
  4. customThe residue was purified by radial chromatography (0-60% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-f1ddf3f3144946caaae32af3611bc827
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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