Hydrochloric Acid → (R)-2-(1-hydroxypropan-2-yl)-6-methyl-5-nitroisoquinolin-1(2H)-one

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Reaction Steps

A round bottom flask was charged with potassium tert-Butoxide (3.62 g, 0.0322 mol) and N,N-dimethylformamide (100 mL, 1 mol) and a solution of acetic acid, chloro-, 1,1-dimethylethyl ester (1.3 mL, 0.0089 mol) and (R)-2-(1-hydroxypropan-2-yl)-5-nitroisoquinolin-1(2H)-one (2.00 g, 0.00806 mol) in N,N-dimethylformamide (20 mL, 0.2 mol) was added at −20° C. dropwise over a period of 8 minutes and the reaction was stirred for an additional 45 minutes at the same temperature. The reaction mixture was poured onto 4 ml of hydrochloric acid and 80 mL of water, and extracted with dichloromethane, washed with brine and dried. the solvent was removed under reduced pressureunder reduced pressure and the residue was used in the next reaction without purification (two isomers in the ratio of 3:1). The residue was treated with trifluoroacetic acid (10 mL, 0.1 mol) for 30 minutes and the trifluoroacetic acid was removed under reduced pressure. The residue was stirred with potassium carbonate (2.2 g, 0.016 mol) in N,N-dimethylformamide (10 mL) at 50° C. for 1 hour. The reaction mixture was cooled and diluted with ethyl acetate (400 mL), washed with 6 N hydrochloric acid (50 mL×4) and the brine (50 mL×2), and dried. The volatiles were removed under reduced pressure and the residue was purified by column chromatography to afford the product as a yellow solid.

Provenance & Evidence