Cesium carbonate → Methyl 2-[5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl]propanoate
Reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=2.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:24]([CH3:29])[C:25]([O:27][CH3:28])=[O:26]>CN(C=O)C>[C:15]([C:7]1[C:8]([C:11]([F:12])([F:14])[F:13])=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]([CH:24]([CH3:29])[C:25]([O:27][CH3:28])=[O:26])[C:2]([CH3:1])=[CH:10]2)#[N:16]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
A mixture of 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (see, for example, US2008139631A1) (0.300 g, 1.338 mmol), cesium carbonate (0.654 g, 2.007 mmol) and methyl 2-bromopropanoate (0.223 mL, 2.007 mmol) in DMF (3 mL) was heated at 90° C. for 1 h. Upon cooling, the reaction mixture was partitioned between Et2O (30 mL) and water (25 mL). The organic phase was washed with water (20 mL) and brine (10 mL). The combined aqueous phases were washed with Et2O (2×25 ml). The organic phases were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel eluting with 5-40% EtOAc-hexane gradient to give methyl 2-[5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl]propanoate (0.419 g, 94% yield): MS (ESI): m/z 311 (MH+).
Workup
- temperatureUpon cooling
- customthe reaction mixture was partitioned between Et2O (30 mL) and water (25 mL)
- washThe organic phase was washed with water (20 mL) and brine (10 mL)
- washThe combined aqueous phases were washed with Et2O (2×25 ml)
- washwashed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was chromatographed over silica gel eluting with 5-40% EtOAc-hexane gradient
Sources & evidence
- ORD record
- ord-3e670e0788bd4abb9b09bb1baa1f9d45
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08957104B2
Reaction notes
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