Piperidine → acetic acid 1-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-ylcarbamoyl)-1-methyl-ethyl ester

HRID 2191418

Reaktionsgleichung

Reaktionsgleichung von HRID 2191418
[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]([C:22]([O:25][C:26](=[O:28])[CH3:27])([CH3:24])[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]([C:22]([O:25][C:26](=[O:28])[CH3:27])([CH3:24])[CH3:23])=[O:21])[NH:8][C:7](=[O:11])[CH2:6]2

Komponenten

5

Edukt 3

HCID 8082PiperidineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 101035046-Amino-5-fluoroindolin-2-one

Produkt 1

HCID 59250100acetic acid 1-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-ylcarbamoyl)-1-methyl-ethyl esterAusbeute 109 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

5-Fluoro-6-amino-1,3-dihydro-indol-2-one 3d (410 mg, 2.47 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 piperidine (322 μl). A solution of acetic acid 1-chlorocarbonyl-1-methyl-ethyl ester (423 mg, 2.71 mmol) in tetrahydrofuran (10 ml) 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 acetic acid 1-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-ylcarbamoyl)-1-methyl-ethyl ester 9a (792 mg) as a white solid to the next step.

Aufarbeitung

  1. temperatureThe mixture was cooled down to −45° C. in a dry ice-acetone bath
  2. additionUpon completion of the addition
  3. customthe ice-acetone bath was removed
  4. temperatureto warm up to room temperature
  5. stirringstirred overnight
  6. filtrationthe reaction mixture was filtered
  7. washThe filter cake was washed with water
  8. customthe resulting solid was dried

Quellen und Nachweise

ORD-Eintrag
ord-51c8b03497c94e96a239b0a6b1660b97
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08329682B2

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