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

HRID 2191447Notes

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].N1C=CC=CC=1.Cl[C:20]([CH2:22][O:23][C:24](=[O:26])[CH3:25])=[O:21]>O1CCCC1>[F:12][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[NH:1][C:20]([CH2:22][O:23][C:24](=[O:26])[CH3:25])=[O:21])[NH:8][C:7](=[O:11])[CH2:6]2

Participants

Conditions

Temperature: -40 °C

Procedure

6-Amino-5-fluoro-1,3-dihydro-indol-2-one 3d (500 mg, 3.0 mmol) was dissolved in 10 ml of tetrahydrofuran under stirring, and added with 0.4 ml of pyridine to the solution at room temperature. After stirring to mix well, the mixture was cooled down to −40° C. in a dry ice-acetone bath. A solution of acetic acid chlorocarbonylmethyl ester (420 mg, 3.0 mmol) in 10 ml of tetrahydrofuran was added dropwise to the above reaction system. Upon completion of the addition, the dry 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 resulting solid was washed with water for three times and dried to obtain the title compound acetic acid (5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-ylcarbamoyl)-methyl ester 27a (562 mg, yield 70.4%) as a gray solid.

Workup

stirringAfter stirring
additionto mix well
additionUpon completion of the addition
customthe dry ice-acetone bath was removed
temperatureto warm up to room temperature
stirringstirred overnight
filtrationthe reaction mixture was filtered
washThe resulting solid was washed with water for three times
customdried

Sources & evidence

ORD record: ord-a859b34d98264d77a571d29e6cc4ff77
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329682B2

Reaction notes

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