Nitric Acid → 1-(4-Fluoro-5-nitroindolin-1-yl)ethan-1-one

HRID 880509Notes

Reaction equation

[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH2:9][N:10]2[C:15](=[O:17])[CH3:16].C(=O)(O)[O-].[Na+]>S(=O)(=O)(O)O>[F:5][C:6]1[C:14]([N+:1]([O-:4])=[O:2])=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH2:9][N:10]2[C:15](=[O:17])[CH3:16]

Participants

Conditions

Temperature: 0 °C

Procedure

Fuming nitric acid (0.22 mL) was added dropwise to a solution of 1-(4-fluoro-indolin-1-yl)ethanone (1 g, 5.58 mmol) in concentrated sulfuric acid (10 mL) at −15° C. to 0° C. The reaction mixture was stirred at 0° C. for 2 h and then the resulting mixture was basified with sodium bicarbonate solution (100 mL). The reaction mixture was partitioned between chloroform (100 mL) and water (100 mL). The organic layer was separated and the aqueous layer was extracted with chloroform (5×30 mL). The combined organic layers were washed with water (3×20 mL), brine (3×20 mL), dried over anhydrous sodium sulphate and concentrated in vacuo to give the crude product. Purification by column chromatography over neutral alumina using 10-12% ethyl acetate in hexane as eluent afforded 1-(4-fluoro-5-nitro-indolin-1-yl)ethanone (0.56 g, 45%) as a yellow solid.

Workup

customThe reaction mixture was partitioned between chloroform (100 mL) and water (100 mL)
customThe organic layer was separated
extractionthe aqueous layer was extracted with chloroform (5×30 mL)
washThe combined organic layers were washed with water (3×20 mL), brine (3×20 mL)
dry with materialdried over anhydrous sodium sulphate
concentrationconcentrated in vacuo
customto give the crude product
customPurification by column chromatography over neutral alumina using 10-12% ethyl acetate in hexane as eluent

Sources & evidence

ORD record: ord-2269dd8d0836433fbe7cdff5870c9e56
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993574B2

Reaction notes

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