Acetic Acid → HCID 9817445, compound

Participants

Reaction Steps

3,4,5,6,7,8-Hexahydro-3-hydroxymethyl-6-((4-methoxyphenyl)methyl)quinolin-2[1H]-one (24.7 g) (prepared according to step c) in THF (200 ml) was treated with borane-dimethylsulphide complex (25 ml) and stirred at room temperature under argon for 18 hours. The reaction mixture was then treated with aqueous acetic acid (20%) until pH 5 and then stirred for an hour. HCl was added until the mixture was strongly acidic and then the solvent removed in vacuo. The residue was dissolved in methanol, concentrated to remove borate esters then converted to the hydrochloride salt (28 g). This salt was recrystallised from ethyl acetate-methanol (200 ml-15 ml) to yield a fraction (15.7 g) containing 34% of the title compound. This fraction was triturated with ethyl acetate, converted to the free base and fractionally crystallised from t-butylmethyl ether, yielding a fraction containing 84% of the title compound. Further recrystallisation was carried out from t-butylmethyl ether diethylether (1:1) and the product converted to the hydrochloride salt (1.8 g), mp 288°-289.5° C.

Provenance & Evidence