Reaction equation
[CH3:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH2:20][CH2:21][Cl:22].O>C(#N)C>[Cl:22][CH2:21][CH2:20][CH2:19][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:2]([CH3:1])[C:3]1=[O:11]Participants
Procedure
To a mixture of 3-methylindolin-2-one (1 g, 6.79 mmol, 1 equiv) in acetonitrile, potassium carbonate (1.877 g, 13.58 mmol, 2.5 equiv) followed by 1-bromo-3-chloropropane (2.01 ml, 20.38 mmol, 3 equiv) were added. The reaction was refluxed for 16 h. Upon cooling water was added and the mixture was extracted into ethyl acetate. The organic layer was further washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (SNAP 100 g cartridge, Rf=0.5, gradient—2%-20% ethyl acetate in hexanes) to afford the title compound as a yellow oil (230 mg, 15%); 1H NMR (400 MHz, DMSO-d6): δ 1.31 (d, 3H, J=7.6 Hz); 1.99-2.05 (m, 2H); 3.47-3.53 (m, 1H); 3.66 (t, 2H, J=6.4 Hz); 3.74-3.82 (m, 2H); 7.04 (d, 2H; J=7.6 Hz); 7.24-7.27 (m, 1H); 7.3-7.32 (m, 1H); MS for C12H14ClNO m/z 211.06 (M+H)+.
Workup
- additionwere added
- temperatureThe reaction was refluxed for 16 h
- additionwas added
- extractionthe mixture was extracted into ethyl acetate
- washThe organic layer was further washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude residue was purified
Sources & evidence
- ORD record
- ord-92d742d7c016498fa79ef20eb6cd9057
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09156840B2
Linked notes
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