Acetic Acid → 1-(7-Bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethanone

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Reaction Steps

Concentrated sulfuric acid (35 mL) was added to glacial acetic acid (45mL) with stirring and ice-cooling. After stirring for 30 minutes the mixture was treated with N-2-(4-bromophenyl)ethyl trifluoroacetamide (10.4 g, Reference Example 8) and then with paraformaldehyde (1.75 g). This mixture was allowed to warm to room temperature and after stirring for a further 24 hours the pale brown solution was treated with a further aliquat of paraformaldehyde (0.8 g). After stirring for a further 24 hours the reaction mixture was treated with iced-water (500 mL) and then extracted three times with ethyl acetate (200 mL). The combined extracts were washed twice with water (200 mL), then four times with aqueous sodium bicarbonate solution (200 mL), then twice with water (200 mL), then dried over magnesium sulfate and then evaporated. The residual yellow oil was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (3:97, v/v) to give the title compound as a white crystalline solid. LC-MS: RT=4.76 minutes; no molecular ion observed.

Provenance & Evidence