1,1,1-Trimethoxy-2-methylpropane → 4,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiaze pine

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Reaction Steps

A solution of 5.86 g of 2-amino-N-methyl-α-(3-methyl-2-thienyl)benzeneethanamine and 19.56 g of trimethyl orthoisobutyrate was treated rapidly with 7.94 ml of glacial acetic acid. The solution was refluxed for 8 hours under nitrogen and concentrated on a rotary evaporator at 40° C. The residual oil was acidified with 10% hydrochloric acid solution and extracted with ether (3×100 ml). The aqueous phase was basified with 10% sodium hydroxide solution and extracted with dichloromethane (3×100 ml). The organic phases was dried over anhydrous sodium sulfate, filtered and concentrated to an oil. Purification was accomplished by HPLC (Water's Associates Prep LC/System 500A, silcia gel, utilizing methanol followed by 2% triethylamine in methanol as successive eluents). Concentration of the appropriate fractions yielded 1.88 g of 4,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiaze pine as an oil. The oil was treated with ethereal hydrogen chloride and the resulting precipitate was triturated with ether to yield 1.80 g of 4,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiazepine hydrochloride, mp 240.5°-241.0° C.

Provenance & Evidence