330156-49-5

Usage

Uses

Used in Organic Synthesis:
(1S)-2-Chloro-1-(2,4-difluorophenyl)ethanol is used as a building block in organic synthesis for the creation of various biologically active compounds. Its unique structure, including the presence of a chiral center, makes it a valuable intermediate in the synthesis of pharmaceuticals and other specialty chemicals.
Used in Pharmaceutical Research:
In the pharmaceutical industry, (1S)-2-Chloro-1-(2,4-difluorophenyl)ethanol is utilized as a key intermediate in the development of new drugs. Its structural features, such as the chlorine and fluorine atoms, can be leveraged to enhance the pharmacological properties of the resulting compounds, potentially leading to improved therapeutic effects and selectivity.
Used in Chemical Research:
(1S)-2-Chloro-1-(2,4-difluorophenyl)ethanol is also employed in chemical research to study the effects of stereochemistry on the reactivity and properties of molecules. Understanding these effects can contribute to the design of more efficient and selective synthetic routes, as well as the development of novel compounds with tailored properties for specific applications.

Upstream product

• 51336-94-8 2-chloro-1-(2,4-dichlorophenyl)ethanone 
• 364-83-0 2',4'-difluoroacetophenone 
• 51336-96-0 2-chloro-1-(2’,4’-difluorophenyl)ethanol 

Downstream Products

• 782482-50-2 (1S)-2-(tert-butylamino)-1-(2,4-difluorophenyl)ethanol 
• 934989-37-4 C₁₃H₁₇F₂NO₂ 
• 852305-05-6 ethyl N-(tert-butyl)-N-[(2S)-2-(2,4-difluorophenyl)-2-hydroxyethyl]-β-alaninate 
• 782482-51-3 3-{tert-butyl[(2S)-2-(2,4-difluorophenyl)-2-hydroxyethyl]amino}propanenitrile 
• 794500-77-9 (3R,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonitrile 
• 794500-76-8 (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonitrile 

Relevant academic research and scientific papers

Lipase mediated enzymatic kinetic resolution of phenylethyl halohydrins acetates: A case of study and rationalization

Racemic phenylethyl halohydrins acetates containing several groups attached to the aromatic ring were resolved via hydrolysis reaction in the presence of lipase B from Candida antarctica (Novozym 435). In all cases, the kinetic resolution was highly selective (E > 200) leading to the corresponding (S)-β-halohydrin with ee > 99 %. However, the time required for an ideal 50 % conversion ranged from 15 min for 2,4-dichlorophenyl chlorohydrin acetate to 216 h for 2-chlorophenyl bromohydrin acetate. Six chlorohydrins and five bromohydrins were evaluated, the latter being less reactive. For the β-brominated substrates, steric hindrance on the aromatic ring played a crucial role, which was not observed for the β-chlorinated derivatives. To shed light on the different reaction rates, docking studies were carried out with all the substrates using MD simulations. The computational data obtained for the β-brominated substrates, based on the parameters analysed such as NAC (near attack conformation), distance between Ser-O and carbonyl-C and oxyanion site stabilization were in agreement with the experimental results. On the other hand, the data obtained for β-chlorinated substrates suggested that physical aspects such as high hydrophobicity or induced change in the conformation of the enzymatic active site are more relevant aspects when compared to steric hindrance effects.

Iridium-Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins

Iridium-catalyzed asymmetric hydrogenation of prochiral halogenated ketones was successfully developed to prepare various chiral halohydrins with high reactivities and excellent enantioselectivities under basic reaction condition (up to >99% conversion, 99% yield, >99% ee). Moreover, gram-scale experiment was performed well in the presence of just 0.005 mol% (S/C=20 000) Ir/f-amphox catalyst with 99% yield and >99% ee. (Figure presented.).

Selective Asymmetric Transfer Hydrogenation of α-Substituted Acetophenones with Bifunctional Oxo-Tethered Ruthenium(II) Catalysts

A practical method for the asymmetric transfer hydrogenation of α-substituted ketones was developed utilizing oxo-tethered N-sulfonyldiamine-ruthenium complexes. Reduction by HCO2H and HCO2K in a mixed solvent of EtOAc/H2O allowed for the selective synthesis of halohydrins from 2-bromoacetophenone (98%) and 2-chloroacetophenone (>99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO2H and Et3N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of α-sulfonated ketones without eroding the leaving group. (Figure presented.).

Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of enantiopure aromatic alcohols

Enzymatic synthesis of enantiopure aromatic secondary alcohols (including substituted, hetero-aromatic and bicyclic structures) was carried out using halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This enzyme showed an unprecedented substrate scope and absolute enatioselectivity. The cofactor NADPH was used catalytically and regenerated in situ by the biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the conversion of aromatic ketones was markedly influenced by the steric and electronic factors as well as the solubility of ketones in the reaction medium. Furthermore, carbonyl stretching band frequencies ν (CO) have been measured for different ketones to understand the effect of electron withdrawing or donating properties of the ketone substituents on the reaction rate catalyzed by HvADH2. Good correlation was observed between ν (CO) of methyl aryl-ketones and the reaction rate catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.

Preparative access to medicinal chemistry related chiral alcohols using carbonyl reductase technology

Libraries of highly enantioenriched secondary alcohols in both enantiomeric forms were synthesised by enzymatic reduction of their parent ketones using selectAZyme carbonyl reductase (CRED) technology. Commercially available CREDs were able to reduce a range of substrate classes efficiently and with very high enantioselectivity. Matching substrate classes to small subsets of CREDs enabled the fast development of preparative bioreductions and the rapid generation of 100-1500 mg samples of chiral alcohols in typically >95% ee and the majority in ≥99.0% ee. The conditions for small scale synthesis were then scaled up to 0.5 kg to deliver one of the chiral alcohols, (S)-1-(4-bromophenyl)-2-chloroethanol, in 99.8% ee and 91% isolated yield.

Novel dimethoxy(aminoalkoxy)borate derived from (S)-diphenylprolinol as highly efficient catalyst for the enantioselective boron-mediated reduction of prochiral ketones

The novel dimethoxyl(aminoalkoxy)borate 1 was isolated as a white crystalline dimer joined by H-bonding as evidenced by X-ray analysis, and demonstrated to be a highly effective catalyst for the asymmetric reduction of representative prochiral ketones with borane-DMS. Optically pure alcohols were obtained using only 1 mol % of catalyst 1 in up to 99% ee.

ACYLATED PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS

Certain novel N-acylated spiropiperidine derivatives are ligands of the human melanocortin receptor(s) and, in particular, are selective ligands of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevent

Enantioselective reduction of prochiral ketones using spiroborate esters as catalysts

Novel spiroborate esters derived nonracemic 1,2-aminoalcohols and ethylene glycol are reported as highly effective catalysts for the asymmetric borane reduction of a variety of prochiral ketones with borane-dimethyl sulfide complex at room temperature. Optically active alcohols were obtained in excellent chemical yields using 0.1-10 mol % of catalysts with up to 99% ee.

ACYLATED SPIROPIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS

Certain novel N-acylated spiropiperidine derivatives are ligands of the human melanocortin receptor(s) and, in particular, are selective ligands of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of MC-4R, such as obesity, diabetes, nicotine addiction, alcoholism, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

ACYLATED PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS

Certain novel N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention