108813-08-7

Upstream product

• 186581-53-3 diazomethane 
• 34385-92-7 2-(4-chlorophenoxy)butanoic acid 
• 106-48-9 4-chloro-phenol 
• 64102-28-9 2-(4-Chloro-phenoxy)-butyric acid ethyl ester 
• 56895-14-8 2-(4-Chlorophenoxy)butyric acid chloride 

Relevant academic research and scientific papers

Direct resolution of α-monoalkyl-α-aryloxyacetic acids via ester or imide derivatives

This paper describes a simple procedure for the resolution of racemic α-monoalkyl α-aryloxyacetic acids, using the chromatographic separation of their covalent derivatives. (R)-Ethyl mandelate, (R)-pantolactone and (S)-4-(1-methylethyl)-2-oxazolidinone are the resolving agents involved in the formation of equimolecular diastereomeric mixtures of esters or imides. Chromatographic resolutions were performed by means of gas chromatography (GC), thin-layer chromatography (TLC) and flash chromatography. Successive hydrolysis of separated diastereomers provided optically pure aryloxyacetic acids.

OXA-SPIRODIPHOSPHINE LIGAND AND METHOD FOR ASYMMETRIC HYDROGENATION OF alpha, beta-UNSATURATED CARBOXYLIC ACIDS

The present invention provides an oxa-spirodiphosphine ligand having a structure of general Formula (I) below: wherein in general Formula (I), R1, R2, R3 and R4 are the same, and are alkyl, alkoxy, aryl, aryloxy

Oxa-spiral diphosphine ligand and application thereof in alpha, beta-unsaturated carboxylic acid asymmetric hydrogenation

The invention provides an oxa-spiral diphosphine ligand. The oxa-spiral diphosphine ligand has a structure shown by a general formula (I) as shown in description, wherein R1, R2, R3 and R4 in the general formula (I) are same and are alkyl, alkoxy, aryl, aroxyl, or hydrogen atoms; R1, R2, R3 and R4 comprise forms of ring formation, non-ring formation, any two ring formation or multiple-ring formation between pairs; R5 and R6 are alkyl, aryl or hydrogen atoms; and R7 and R8 are alkyl or benzyl or aryl. The invention further provides application of the oxa-spiral diphosphine ligand O-SDP in the alpha, beta-unsaturated carboxylic acid asymmetric hydrogenation. A complex of the oxa-spiral diphosphine ligand O-SDP and ruthenium has excellent activity and enantioselectivity in the asymmetric hydrogenation of the alpha, beta-unsaturated carboxylic acid in multiple types, and a chiral carboxylic acid product is obtained with the enantioselectivity being up to 99%. The synthesis method can be applied to the construction of a core skeleton of chemical molecules with important activity, wherein the chemical molecules comprise Paroxetine, Femoxetine, nipecotic acid and Sacubitril.

Enantioselective hydrogenation of α-aryloxy and α-alkoxy α,β-unsaturated carboxylic acids catalyzed by chiral spiro iridium/phosphino-oxazoline complexes

The iridium-catalyzed highly enantioselective hydrogenation of α-aryloxy and α-alkoxy-substituted α,β-unsaturated carboxylic acids was developed. By using chiral spiro phosphino-oxazoline ligands, the hydrogenation proceeded smoothly to produce various α-aryloxy- and α-alkoxy-substituted carboxylic acids with extremely high enantioselectivities (ee up to 99.8%) and reactivities (TON up to 10 000) under mild conditions. The hydrogenation of R-benzyloxy-substituted α,β-unsaturated acids provided an efficient alternative for the synthesis of chiral R-hydroxy acids after an easy deprotection. A mechanism involving a catalytic cycle between IrI and IrIII was proposed on the basis of the coordination model of the unsaturated acids with the iridium metal center. The rationality of the catalytic cycle, with an olefin dihydride complex as the key intermediate, was supported by the deuterium-labeling studies. The X-ray diffraction analysis of the single crystal of catalyst revealed that the rigid and sterically hindered chiral environment created by the spiro phosphino-oxazoline ligands is the essential factor that permits the catalyst to obtain excellent chiral discrimination. A chiral induction model was suggested on the basis of the catalyst structure and the product configuration.

Asymmetric hydrogenation of α,β-unsaturated carboxylic acids catalyzed by ruthenium(II) complexes of spirobifluorene diphosphine (SFDP) ligands

The ruthenium diacetate complexes ligated by chiral spirobifluorene diphosphines (SFDP) were very effective catalysts for the asymmetric hydrogenation of tiglic acid derivatives and α-methylcinnamic acid derivatives with high activities and excellent enantioselectivities (up to 98% ee). The α-aryloxybutenoic acids can also be hydrogenated by these catalysts to provide the corresponding saturated α-aryloxybutanoic acids in high yields (89-93%) and enantioselectivities (up to 95% ee). In this reaction, the SFDP ligand with para-methyl groups on the P-phenyl rings gave the best results.

Candida cylindracea lipase-mediated kinetic resolution of α-substituted α-aryloxyacetic acid methyl esters

Hydrolysis of several α-alkyl-α-aryloxyacetic acid methyl esters and of α-methyl-α-(n-propyl)-α-(p-chlorophenoxy)acetic acid methyl ester were performed in the presence of Candida cylindracea lipase. The α-alkyl-α-aryloxyacetic acid methyl esters and α-methyl-α-(n-propyl)-α-(p-chlorophenoxy)acetic acid methyl ester were incubated in buffer phosphate (pH 7-8). The reaction mixture, containing the unreacted ester and corresponding acid, showed enantiomeric excesses (ee) up to 81%. The extent of conversion was quite low for the α-methyl-α-(n-propyl)-α-(p-chlorophenoxy)acetic acid methyl ester, the corresponding acid was obtained with ee > 98%.

Stereospecificity of the Chloride Ion Channel: The Action of Chiral Clofibric Acid Analogues

2-(p-Chlorophenoxy)isobutyric acid (clofibric acid (1) or CPIB) is a drug known to block chloride membrane conductance (GCl) in rat striated muscle.In the present study chiral analogues of CPIB (2-(p-chlorophenoxy)propionic acid (2) and 2-(p-chlorophenoxy)butyric acid (3)) have been tested to evaluate the influence of chirality on Cl ion flux in the channel.The results showed that the chloride channel conductance strongly depends on the absolute configuration: in fact, the S-(-) isomers of the tested compounds strongly decreased the GCl of skeletal muscle membrane, whereas the R-(+) isomers were virtually ineffective.These data allow the hypothesis that, like other ion channels present in various biological systems, the chloride channel of skeletal muscle membrane could also have a stereospecific binding site (or receptor) regulating chloride ion flux.