Methyl iodide → 5-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one

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Reaction Steps

To a solution of 3-fluoro-2-(2-methoxycarbonylamino-ethyl)-6-nitro-benzoic acid methyl ester (20.4 g, 68 mmol) in THF (200 mL), sodium hydride (5.44 g, 136 mmol) was added at 0° C. and the mixture was stirred at rt for 2.0 hrs. To the reaction mixture was added methyl iodide (12.7 mL, 204 mmol) at 0° C. and the mixture was stirred at rt for 1.5 hours. To the mixture was added saturated ammonium chloride solution at 0° C., and the mixture was extracted three times with ethyl acetate. The organic layer was washed twice with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (dichloromethane/ethyl acetate/hexane: from 99/1/50 to 99/2/50) to give 5-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one (10.9 g) as yellow solid in 71% yield.

Provenance & Evidence