Asymmetric synthesis of 5-hydroxytryptamine receptor agonist(1R,2S)-(-)-2-( 2-hydroxyphenyl)-N,N-dipropylcyclopropamine

The synthesis of the potent 5-HT receptor agonist(1R, 2S)-(-)-2- (2-hydroxy phenyl)-N, N-propylcyclopropamine was described in this paper. Asymmetric c yclopropanation of 8-methoxystyrene with (dicyclohexyl) methyl diazoacetate in the presence of 1 % (molar fraction) copper(I) triflate and bis(oxazoli ne) ligand gave chiral cyclopropane-1-carboxylate. After selecting alkaline hydrolysis, trans-cyclopropane-l-carboxylic acid was obtained. The subsequ ent Curtius rearrangement and hydrolysis in dilute hydrochloric acid were a ccomplished to yield the(1R,2S)-(-)-2-(2-methoxyphenyl)cyclopropylamine. N, N-Dialkylation with n-propyliodide and demethylation by 48% aq. HBr provide d the desired optically pure (1R,2S)-(-)-2- (2-hydroxyphenyl)-N, N-dipropyl cyclopropylamine.