Isopropyl iodide → 2,2,2-trifluoro-1-(6-bromo-1-isopropyl-1H-indol-3-yl)-ethanone
Reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Br:14])=[CH:11][CH:12]=2)[NH:7][CH:6]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].I[CH:24]([CH3:26])[CH3:25]>CN(C)C=O>[F:16][C:2]([F:1])([F:15])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Br:14])=[CH:11][CH:12]=2)[N:7]([CH:24]([CH3:26])[CH3:25])[CH:6]=1)=[O:4]Participants
Conditions
- Temperature
- 25 °C
Procedure
A solution of 2,2,2-trifluoro-1-(6-bromo-1H-indol-3-yl)-ethanone (3.0 g, 10.27 mmol) in N,N-dimethylformamide (20 mL) at 25° C. was treated with potassium carbonate (3.54 g, 25.68 mmol). The resulting mixture was stirred at 25° C. for 15 min and then treated with 2-iodopropane (1.54 mL, 15.41 mmol). The reaction was heated at 65° C. for 18 h. At this time, the reaction was cooled to 25° C. and was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic layer was then washed with a 1N aqueous hydrochloric acid solution (1×25 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 2,2,2-trifluoro-1-(6-bromo-1-isopropyl-1H-indol-3-yl)-ethanone (3.38 g, 99%) as a pink solid: mp 77-79° C.; EI-HRMS m/e calcd for C13H11BrF3NO (M) 332.9976, found 332.9975.
Workup
- temperatureThe reaction was heated at 65° C. for 18 h
- temperatureAt this time, the reaction was cooled to 25° C.
- customwas partitioned between water (100 mL) and ethyl acetate (100 mL)
- washThe organic layer was then washed with a 1N aqueous hydrochloric acid solution (1×25 mL)
- dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-72f6cace13f54093bc7e595f9344e536
- Source dataset
- uspto-grants-2005_04
- Patent number
- US06881844B2
Reaction notes
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