Synthetic method of (S)-N,N-dimethyl-3-hydroxyl-3-(2-thiophen)propanamine

(s)-n,n-二甲基-3-羟基-3-(2-噻吩基)丙胺的合成方法

Abstract

The invention provides a method for synthesizing (S)-N, N-dimethyl-3-hydroxyl-3-(2-thienyl) propylamine, and relates to a key intermediate of (S)-duloxetine. The method for synthesizing the (S)-N, N-dimethyl-3-hydroxyl-3-(2-thienyl) propylamine comprises the following steps: dissolving chiral diaminodiphosphine-ruthenium catalyst (III) in an organic solvent under nitrogen atmosphere; respectively adding organic hydrogen source isopropanol and an alkaliferous solution, and adding 3-dimethylamino-1-(2-thienyl)-1-acetone (II) to the mixed solvent at a temperature of between 20 and 82 DEG C so as to react to obtain the target product (S)-N, N-dimethyl-3-hydroxyl-3-(2-thienyl) propylamine (I). The method has the advantages of mild reaction condition, simple and safe operation, easy synthesis of the chiral catalyst and low cost, and the enantioselectivitiy of the product reaches 98 percent ee, and the optical purity of the product can be compared favorably to a split method. The invention provides a new effective and feasible way for industrial production of (S)-duloxetine.
(S)-N,N-二甲基-3-羟基-3-(2-噻吩基)丙胺的合成方法,涉及一种(S)-度洛西汀的关键中间体。提供一种(S)-N,N-二甲基-3-羟基-3-(2-噻吩基)丙胺的合成方法。将手性双胺双膦-钌催化剂(III)在氮气氛下溶于有机溶剂中,在20~82℃下,分别加入有机氢源异丙醇和含碱的溶液,再加入3-二甲胺基-1-(2-噻吩基)-1-丙酮(II),反应得目标产物(S)-N,N-二甲基-3-羟基-3-(2-噻吩基)丙胺(I)。反应条件温和、操作简便安全、手性催化剂易于合成、成本低,产物的对映选择性高达98%ee,光学纯度可与拆分方法相媲美;为工业化生产(S)-度洛西汀提供有效可行的新路径。

Claims

Description

Topics

Download Full PDF Version (Non-Commercial Use)

Patent Citations (0)

    Publication numberPublication dateAssigneeTitle

NO-Patent Citations (0)

    Title

Cited By (1)

    Publication numberPublication dateAssigneeTitle
    CN-102532097-AJuly 04, 2012华东理工大学Asymmetric synthesis method of duloxetine intermediate-(S)-N, N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamine