Piperidine → acetic acid 1-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-ylcarbamoyl)-ethyl ester
Reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][C:3]=1[F:12].N1CCCCC1.Cl[C:20]([CH:22]([O:24][C:25](=[O:27])[CH3:26])[CH3:23])=[O:21]>O1CCCC1>[F:12][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[NH:1][C:20]([CH:22]([O:24][C:25](=[O:27])[CH3:26])[CH3:23])=[O:21])[NH:8][C:7](=[O:11])[CH2:6]2Participants
Procedure
5-Fluoro-6-amino-1,3-dihydro-indol-2-one 3d (450 mg, 2.71 mmol) was dissolved in 10 ml of tetrahydrofuran under stirring at room temperature. The mixture was cooled down to −45° C. in a dry ice-acetone bath and added with 364 μl of piperidine. A solution of acetic acid 1-chlorocarbonyl-ethyl ester (423 mg, 2.71 mmol) in 10 ml of tetrahydrofuran was added dropwise to the above reaction system. Upon completion of the addition, the ice-acetone bath was removed, and the reaction mixture was allowed to warm up to room temperature and stirred overnight. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was filtered. The filter cake was washed with water, and the resulting solid was dried to obtain the title compound acetic acid 1-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-ylcarbamoyl)-ethyl ester 8a (840 mg) as a white solid to be used directly in the next step.
Workup
- temperatureThe mixture was cooled down to −45° C. in a dry ice-acetone bath
- additionUpon completion of the addition
- customthe ice-acetone bath was removed
- temperatureto warm up to room temperature
- stirringstirred overnight
- filtrationthe reaction mixture was filtered
- washThe filter cake was washed with water
- customthe resulting solid was dried
Sources & evidence
- ORD record
- ord-ecc1b338a9f840889d38ed3ddb1afa1d
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329682B2
Reaction notes
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