Hydrochloric Acid → 6-Methyl-5-nitro-1H-isochromen-1-one

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Reaction Steps

Alternatively, to a solution of potassium tert-butoxide (8.72 g, 0.0777 mol) in N,N-dimethylformamide (250 mL, 3.2 mol) was added a mixture of acetic acid, chloro-, 1,1-dimethylethyl ester (4.335 g, 0.02878 mol) and 5-nitro-1H-isochromen-1-one (5.0 g, 0.026 mol) in N,N-dimethylformamide (50 mL, 0.6 mol) at −20° C. After 1 h, the reaction was poured onto hydrochloric acid (16 mL) and water (35 mL). The aqueous solution was extracted with dichloromethane, washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was treated with trifluoroacetic acid (35 mL, 0.45 mol ) for 0.5 h and was removed under reduced pressure. The residue was stirred with potassium carbonate (6.98 g, 0.0505 mol) in N,N-dimethylformamide (200 mL, 2 mol) at 50° C. for 1 h. The reaction was cooled and added with 1 N hydrochloric acid (262 mL), extracted with dichloromethane (80 mL×3), washed with brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the mixture was purified by flash chromatography to afford the title compound as a yellow solid.

Provenance & Evidence