Asymmetric Synthesis of 5-Hydroxytryptamine Receptor Agonist(1R,2S)-(-)-2-(2-hydroxyphenyl)-N,N-dipropylcyclopropamine

Abstract

Abstract: The synthesis of the potent 5-HT receptor agonist(1R,2S)-(-)-2-(2-hydroxyphenyl)-N,N-propylcyclopropamine was described in this paper. Asymmetric cyclopropanation of 2-methoxystyrene with(dicyclohexyl)methyl diazoacetate in the presence of 1%(molar fraction) copper(Ⅰ) triflate and bis(oxazoline) ligand gave chiral cyclopropane-1-carboxylate. After selecting alkaline hydrolysis, trans cyclopropane-1-carboxylic acid was obtained. The subsequent Curtius rearrangement and hydrolysis in dilute hydrochloric acid were accomplished to yield the(1R,2S)-(-)-2-(2-methoxyphenyl)cyclopropylamine. N,N-Dialkylation with n-propyliodide and demethylation by 48% aq. HBr provided the desired optically pure(1R,2S)-(-)-2-(2 hydroxyphenyl)-N,Nd-ipropylcyclopropylamine.

Key words: Asymmetric synthesis, Chiral cyclopropylamine, Asymmetric cyclopropanation

CLC Number:

O625

TrendMD:

WU Xin-Yan, SHU Fu-Chang, ZHOU Qi-Lin . Asymmetric Synthesis of 5-Hydroxytryptamine Receptor Agonist(1R,2S)-(-)-2-(2-hydroxyphenyl)-N,N-dipropylcyclopropamine[J]. Chem. J. Chinese Universities, 1999, 20(12): 1892.

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Asymmetric Synthesis of 5-Hydroxytryptamine Receptor Agonist(1R,2S)-(-)-2-(2-hydroxyphenyl)-N,N-dipropylcyclopropamine

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