Acetone → 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-hydroxyethyl)-6-nitro-benzoic acid methyl ester (51.4 g, 0.2 mol) in acetone (1000 mL), 2,2,6,6-tetramethylpiperidine 1-oxyl, Free radical, (460.6 mg, 2.95 mmol), an aqueous 15% solution of sodium hydrocarboxide (400 mL) and sodium bromide (3.02 g, 29.3 mmol) was added. Trichloroisocyanuric acid (68.4 g, 0.29 mol) was then slowly added within 30 min at rt. After completion of the addition and being stirred at rt for 2.5 hrs, 15 mL of isopropanol was added at 0° C. carefully. The mixture was concentrated under reduced pressure. The mixture was extracted three times with ethyl acetate. The organic layer was extracted three times with 1N sodium hydroxide. The combined water layer was washed once with ethyl acetate, then acidified with 5N hydrogen chloride at 0° C. After extraction four times with ethyl acetate, the organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The title compound 2-(2-carboxy-ethyl)-3-fluoro-6-nitro-benzoic acid methyl ester (28.7 g) was obtained as yellow solid in 72% yield (2 steps).

Provenance & Evidence