Acrylonitrile → 3,4-dihydro-2H-1-benzopyran-2-carboxylic acid

Participants

Reaction Steps

An alternative route to the dihydroaminopyran, O, again starting with Aldehyde M, is described in Thorberg et al., supra. Aldehyde M is reacted with acrylonitrile and 1,4-diazabicyclo[2.2.2]octane (DABCO) at reflux. The cyanobenzopyran is converted to the corresponding benzopyran carboxylic acid with aqueous sodium hydroxide. The benzopyran carboxylic acid (Q) is esterified using a mineral acid in ethanol and reduced by hydrogenation over 5% Pd/C to provide a chroman carboxylic acid. The chroman carboxylic acid is reacted with diphenylphosphorazidate and trimethylamine in benzene at reflux followed by addition of benzyl alcohol and an additional 24 hours at reflux. This provides a benzyloxycarbonyl (SOC) protected amine (R). Hydrogenation of the BOC protected amine provided racemic aminochroman (Q) (Step v). The racemic amine (Q) was resolved using the technique described in WO 93/07135 (Step vi). The resolved (R)-amine (P) is converted to a compound having formula VII following the procedures described in WO 95/11891 (Step vii).

Provenance & Evidence