Acetone → 8-fluoro-4,5-dihydro-3-(3-hydroxy-3-methyl-1-butynyl)-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

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Reaction Steps

1.27 g (5 mmol) of 3-ethynyl-8-fluoro-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one was suspended in 10 ml of tetrahydrofuran and treated dropwise within 20 minutes at a maximum of -5° with 6.4 ml (10 mmol) of 1.6M butyllithium in hexane. After stirring in an ice-bath for 2 hours the mixture was cooled to -70° and there was added thereto in succession 1.7 ml of hexamethylphosphoric acid triamide and 0.6 g (10 mmol) of acetone. The mixture was left to come to room temperature within 4.5 hours, left to stand overnight and poured into about 120 ml of water. After acidification with 4N hydrochloric acid the mixture was extracted four times with ether and six times with ethyl acetate, the combined extracts were dried over magnesium sulphate and evaporated. After chromatography of the residue on silica gel while eluting with ethyl acetate and after crystallization from ethyl acetate there was obtained 8-fluoro-4,5-dihydro-3-(3-hydroxy-3-methyl-1-butynyl)-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one of melting point 163°-164°.

Provenance & Evidence