164071-58-3

Usage

InChI:InChI=1/C7H9IOS/c8-4-3-6(9)7-2-1-5-10-7/h1-2,5-6,9H,3-4H2

Upstream product

• 164071-56-1 (S)-3-chloro-1-(thiophen-2-yl)propan-1-ol 
• 40570-64-7 3-chloro-1-(2-thienyl)propan-1-one 

Downstream Products

• 116539-55-0 (S)-3-methylamino-1-(2-thienyl)-1-propanol 
• 116539-58-3 Duloxetine 

Relevant academic research and scientific papers

Method for preparation of optically active 3-amino-arylpropan-1-ol derivatives from 3-chloro-1-arylpropan-1-ol derivatives

The present invention relates to a method for preparing an optically active 3-amino-1-arylpropan-1-ol derivative, including the step of making an optically active 3-chloro-1-arylpropan-1-ol compound react with an amine derivative. The method according to the present invention allows direct amination of an optically active 3-chloro-1-arylpropan-1-ol derivative through a single-step reaction. Thus, it is possible to provide a compound functioning as a key intermediate of various optically active molecules through a simple process with high yield, while maintaining the optical purity of the reactant. Therefore, the method may be used for preparing medicines, such as (S)-Duloxetin, (R)-Fluoxetine, (R)- Tomoxetine or (R)- Nisoxetine, with high optical purity by combining the method for preparing an optically active 3-chloro-1-arylpropan-1-ol derivative as a reactant of the method with an additional substitution reaction.(AA) Tomoxetine(BB) Fluoxetine(CC) 3-amino-1-propanol(DD) Nisoxetine(EE) DuloxetineCOPYRIGHT KIPO 2016

A method for preparing optically active 3-amino-1-propanol derivatives as an intermediate and a method for preparing (S)-duloxetine using the same

The present invention relates to a method for preparing optically active 3-AMNO1-propanol derivatives as an intermediate and a method for preparing (s)-duloxetine using the same. This method can obtain optically active 3-AMNO1-propanol with higher yield and optical purity (ee) than any other conventional methods. Using this as an intermediate compound, it is possible to manufacture duloxetine which is enantiomerically pure and has high optical purity (ee).(DD) Nisoxetine(EE) Duloxetine(CC) 3-amino-1-propanol(BB) Fluoxetine(AA) TomoxetineCOPYRIGHT KIPO 2015

Copper(ii)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: Asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.

Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake.

A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta) has proven to be effective in clinical trials for the treatment of depression.

An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers

Two 14C-isotopomers of duloxetine HCl (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride), a potent mixed serotonin/norepinephrine Uptake inhibitor have been prepared by an asymmetric synthesis. The palladium catalyzed cross-coupling of 2-thienoyl chloride (3c) (or its [carbonyl-14C] isotopomer 3d) with vinyl tri-n-butylstannane, followed by addition of HCl afforded the key pro-chiral intermediate chloroketone (5a,b). Chiral reduction with borane in the presence of the appropriate oxazaborolidine catalyst (14a or b) provided the S-chloroalcohol (7a) and its 14C-labeled counterpart 7b or the analogous R-chloroalcohol (6). Activation of 7a,b by reaction with NaI/acetone, followed by reaction of the corresponding iodoalcohol with methylamine yielded the penultimate aminoalcohols (8a,b). Formation of the alkoxide with NaH, followed by reaction with 1-fluoronaphthalene yielded duloxetine or its 14C-labeled isotopomer 9. Alternatively, reaction of 6 with 1-naphthol-[1-14C] under Mitsunobu conditions afforded aryl-ether 10a,b, which was in turn activated by reaction with NaI/acetone Subsequent reaction of 10c,d with methylamine followed by salt formation yielded duloxetine or its naphthalene-labeled isotopomer (13) as their HCl salts.