17061-53-9

Usage

Uses

Used in Pharmaceutical Industry:
(R)-1-(3-Chlorophenyl)ethanamine is used as a key intermediate in the synthesis of chirally optically active drugs and compounds. Its unique stereochemistry allows for the development of drugs with specific therapeutic effects and reduced side effects compared to their racemic counterparts.
Used in Chemical Synthesis:
(R)-1-(3-Chlorophenyl)ethanamine serves as a versatile building block in the synthesis of various organic compounds, including pharmaceuticals, agrochemicals, and other specialty chemicals. Its reactivity and functional group compatibility make it a valuable component in the development of new molecules with desired properties.
Used in Research and Development:
As a chiral compound, (R)-1-(3-chlorophenyl)ethanamine is an important tool in research and development for understanding the role of stereochemistry in biological activity and drug design. It can be used to study the interactions between chiral molecules and their targets, as well as to develop new methods for the synthesis of enantiomerically pure compounds.

InChI:InChI=1/C8H10ClN/c1-6(10)7-3-2-4-8(9)5-7/h2-6H,10H2,1H3/t6-/m1/s1

Upstream product

• 2856-63-5 2-Chlorophenylacetonitrile 
• 120121-01-9 1-(m-Chlorophenyl)ethanol 
• 24358-43-8 1-(3-Chloro-phenyl)-ethylamine 
• 1211473-50-5 (R)-N-[(1R)-1-(3-chlorophenyl)ethyl]-2-methylpropane-2-sulfinamide 
• 99-02-5 3'-Chloroacetophenone 
• 141-78-6 ethyl acetate 
• 127733-35-1 1-(3-chlorophenyl)ethan-1-one O-methyl oxime 
• 109-73-9 N-butylamine 
• 124-20-9 N-(3-aminopropyl)-1,4-diaminobutane 

Downstream Products

• 1342278-36-7 (S)-1-(1-(3-chlorophenyl)ethyl)-3-(4-(pyridin-4-yl)thiazol-2-yl)urea 
• 1213318-20-7 (S)-1-(3-chlorophenyl)ethanamine hydrochloride 
• 1025772-35-3 1-(3-bromo-4-chlorophenyl)-N-((R)-1-(3-chlorophenyl)ethyl)ethanamine 
• 1025772-16-0 3-(aminosulfonyl)-4-chloro-N-((1R)-1-(3-chlorophenyl)ethyl)benzamide 
• 1025772-14-8 (R)-3-bromo-4-chloro-N-(1-(3-chlorophenyl)ethyl)benzamide 
• 1025772-17-1 (R)-N-(1-(3-chlorophenyl)ethyl)-4-methoxy-3-(morpholinosulfonyl)benzamide 
• 1025771-23-6 (R)-N-(4-chloro-3-nitrobenzyl)-1-(3-chlorophenyl)ethanamine 
• 1025770-95-9 (R)-N-(2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenyl)-5-methylisoxazole-3-carboxamide 
• 1025772-33-1 (R)-N-(3-(tert-butyldimethylsilyloxy)-4-chlorobenzyl)-1-(3-chlorophenyl)ethanamine 
• 1195985-44-4 (1R)-1-(3-chlorophenyl)-N-((1R)-1-(1-(3-chlorophenyl)-5-methoxy-1H-pyrazol-3-yl)ethyl)ethanamine 
• 1143521-06-5 (1R)-1-(3-chlorophenyl)-N-((1R)-1-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)ethyl)ethanamine 
• 1195985-43-3 (1R)-1-(1-(4-bromophenyl)-5-methoxy-1H-pyrazol-3-yl)-N-((R)-1-(3-chlorophenyl)ethyl)ethanamine 
• 1257090-15-5 (6-bromoquinoxalin-2-yl)-[(R)-1-(3-chlorophenyl)ethyl]amine 
• 1342278-33-4 (R)-1-(1-(3-chlorophenyl)ethyl)-3-(4-(pyridin-4-yl)thiazol-2-yl)urea 

Relevant academic research and scientific papers

A Simple Biosystem for the High-Yielding Cascade Conversion of Racemic Alcohols to Enantiopure Amines

The amination of racemic alcohols to produce enantiopure amines is an important green chemistry reaction for pharmaceutical manufacturing, requiring simple and efficient solutions. Herein, we report the development of a cascade biotransformation to aminate racemic alcohols. This cascade utilizes an ambidextrous alcohol dehydrogenase (ADH) to oxidize a racemic alcohol, an enantioselective transaminase (TA) to convert the ketone intermediate to chiral amine, and isopropylamine to recycle PMP and NAD+ cofactors via the reversed cascade reactions. The concept was proven by using an ambidextrous CpSADH-W286A engineered from (S)-enantioselective CpSADH as the first example of evolving ambidextrous ADHs, an enantioselective BmTA, and isopropylamine. A biosystem containing isopropylamine and E. coli (CpSADH-W286A/BmTA) expressing the two enzymes was developed for the amination of racemic alcohols to produce eight useful and high-value (S)-amines in 72–99 % yield and 98–99 % ee, providing with a simple and practical solution to this type of reaction.

Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2

A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.

n-Butylamine as an alternative amine donor for the stereoselective biocatalytic transamination of ketones

Formal reductive amination has been a main focus of biocatalysis research in recent times. Among the enzymes able to perform this transformation, pyridoxal-5′-phosphate-dependent transaminases have shown the greatest promise in terms of extensive substrate scope and industrial application. Despite concerted research efforts in this area, there exist relatively few options regarding efficient amino donor co-substrates capable of allowing high conversion and atom efficiency with stable enzyme systems. Herein we describe the implementation of the recently described spuC gene, coding for a putrescine transaminase, exploiting its unusual amine donor tolerance to allow use of inexpensive and readily-available n-butylamine as an alternative to traditional methods. Via the integration of SpuC homologues with tandem co-product removal and cofactor regeneration enzymes, high conversion could be achieved with just 1.5 equivalents of the amine with products displaying excellent enantiopurity.

Stereoselective amination of racemic sec-alcohols through sequential application of laccases and transaminases

A one-pot/two-step bienzymatic asymmetric amination of secondary alcohols is disclosed. The approach is based on a sequential strategy involving the use of a laccase/TEMPO catalytic system for the oxidation of alcohols into ketone intermediates, and their following transformation into optically enriched amines by using transaminases. Individual optimizations of the oxidation and biotransamination reactions have been carried out, studying later their applicability in a concurrent process. Therefore, 17 racemic (hetero) aromatic sec-alcohols with different substitutions in the aromatic ring have been converted into enantioenriched amines with good to excellent selectivities (90-99% ee) and conversion values (67-99%). The scalability of the process was also demonstrated when two different amine donors were used in the transamination step, such as isopropylamine and cis-2-buten-1,4-diamine. Satisfyingly, both sacrificial amine donors can shift the equilibrium toward the amine formation, leading to the corresponding isolated enantioenriched amines with good to excellent results.

Biocatalytic transamination with near-stoichiometric inexpensive amine donors mediated by bifunctional mono- and di-amine transaminases

The discovery and characterisation of enzymes with both monoamine and diamine transaminase activity is reported, allowing conversion of a wide range of target ketone substrates with just a small excess of amine donor. The diamine co-substrates (putrescine, cadaverine or spermidine) are bio-derived and the enzyme system results in very little waste, making it a greener strategy for the production of valuable amine fine chemicals and pharmaceuticals.

Biocatalytic Transamination for the Asymmetric Synthesis of Pyridylalkylamines. Structural and Activity Features in the Reactivity of Transaminases

A set of transaminases has been investigated for the biocatalytic amination of 1-(4-chloropyridin-2-yl)alkan-1-ones. The influence of the chain length of the n-1-alkanone at the C-2 position of the pyridine has been studied in the reaction with different

Enantioselective synthesis of (R)-2-arylpropanenitriles catalysed by ene-reductases in aqueous media and in biphasic ionic liquid-water systems

The enantioselective reduction of α-methylene nitrile derivatives catalysed by ene-reductases affords the corresponding (R)-2-arylpropanenitriles with high conversion values. The reaction is investigated either in aqueous medium (with an organic cosolvent or by loading the substrate onto hydrophobic resins) or in a biphasic ionic liquid-water system. The use of ionic liquids, herein with isolated ene-reductases, is found to improve the work-up and the substrate recovery method. The synthetic manipulation of the final chiral nitrile derivatives indicates how this biocatalysed method can be exploited for the preparation of a wide range of chiral compounds.

Microwave-Enhanced Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)imines

Microwave irradiation has considerably enhanced the efficiency of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropyl alcohol catalyzed by a ruthenium complex bearing the achiral ligand 2-amino-2-methylpropan-1-ol. In addition to shortening reaction times for the transfer hydrogenation processes to only 30 min, the amounts of ruthenium catalyst and isopropyl alcohol can be considerably reduced in comparison with our previous procedure assisted by conventional heating, which diminishes the environmental impact of this new protocol. This methodology can be applied to aromatic, heteroaromatic and aliphatic N-(tert-butylsulfinyl)ketimines, leading, after desulfinylation, to the expected primary amines in excellent yields and with enantiomeric excesses of up to 96 %. Microwave irradiation promotes the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in 2-propanol catalysed by a ruthenium complex bearing an achiral β-amino alcohol as ligand. After desulfinylation, α-branched primary amines containing aromatic, heteroaromatic and aliphatic substituents are obtained in excellent yields and with enantiomeric excesses of up to 96 %.

Transaminases applied to the synthesis of high added-value enantiopure amines

Critical parameters affecting the stereoselective amination of (hetero)aromatic ketones using transaminases have been studied, such as temperature, pH, substrate concentration, cosolvent, and source and percentage of amino donor, to further optimize the production of enantiopure amines using both (S)- and (R)-selective biocatalysts from commercial suppliers. Interesting enantiopure amino building blocks have been obtained, overcoming some limitations of traditional chemical synthetic methods. Representative processes were scaled up, affording halogenated and heteroaromatic amines in enantiomerically pure form and good isolated yields.

From racemic alcohols to enantiopure amines: Ru-catalyzed diastereoselective amination

A commercially available ruthenium(II) PNP-type pincer catalyst (Ru-Macho) promotes the formation of α-chiral tert-butanesulfinylamines from racemic secondary alcohols and Ellmans chiral tert-butanesulfinamide via a hydrogen borrowing strategy. The formation of α-chiral tert-butanesulfinylamines occurs in yields ranging from 31% to 89% with most examples giving >95:5 dr.