Methyl iodide → 5-Methoxy-1,3-dimethyl-6-trifluoromethyl-1H-indole
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]([F:15])([F:14])[F:13])[NH:8][CH:7]=[C:6]2[CH3:16].[H-].[Na+].I[CH3:20]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]([F:15])([F:13])[F:14])[N:8]([CH3:20])[CH:7]=[C:6]2[CH3:16]Participants
5
Conditions
- Temperature
- 0 °C
Procedure
A solution of 5-Methoxy-3-methyl-6-trifluoromethyl-1H-indole (900 mg, 4 mmol) in 7 ml DMF was cooled to zero degrees C., and sodium hydride (104 mg, 4 mmol, 95% powder) was added. The reaction mixture was stirred 15 minutes at zero degrees C., and then iodomethane (270 ul, 4 mmol) was added. The reaction mixture was stirred for 1 hour and allowed to warm to room temperature. The reaction mixture was then cooled to 0° C., quenched by addition of 1 N NH4Cl, diluted with water, and extracted with EtOAc. The combined organic layers were washed with water, brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 5-Methoxy-1,3-dimethyl-6-trifluoromethyl-1H-indole (725 mg, 75%) as a solid.
Workup
- stirringThe reaction mixture was stirred for 1 hour
- temperatureto warm to room temperature
- temperatureThe reaction mixture was then cooled to 0° C.
- customquenched by addition of 1 N NH4Cl
- additiondiluted with water
- extractionextracted with EtOAc
- washThe combined organic layers were washed with water, brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-71ab0b64461b4fa1a101d8d171a376b8
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846705B2
Reaction notes
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