159156-84-0

Upstream product

• 137310-16-8 (R)-3-(4-chlorophenyl)-glutaric acid monomethyl ester 
• 104-88-1 4-chlorobenzaldehyde 
• 35271-74-0 3-(4-chlorophenyl)pentane-1,5-dioic acid 
• 137310-14-6 trimethyl 2-(4-chlorophenyl)propane-1,1,3-tricarboxylate 
• 137310-15-7 dimethyl 3-(p-chlorophenyl)glutarate 
• 20754-21-6 methyl 3-(4-chlorophenyl)propenoate 
• 1615-02-7 3-(4-chlorophenyl)prop-2-enoic acid 

Relevant academic research and scientific papers

Optical resolution of baclofen via diastereomeric salt pair formation between 3-(p-chlorophenyl)glutaramic acid and (S)-(-)-α-phenylethylamine

The structures of the diastereomeric salts of (R)-(+)- and (S)-(-)-3-(p-chlorophenyl)glutaramic acid with (S)-(-)-phenylethylamine have been determined by X-ray crystallography. Solubility and melting behaviours of the salts were analysed and correlated with their structural properties in the solid state. The (R)-(+)-3-(p-chlorophenyl)glutaramic acid was converted to (R)-(-)-baclofen via a Hofmann degradation (57% yield, 99.8% ee, enantiomeric excess).

Biocatalytic Desymmetrization of Prochiral 3-Aryl and 3-Arylmethyl Glutaramides: Different Remote Substituent Effect on Catalytic Efficiency and Enantioselectivity

Catalyzed by an amidase-containing Rhodococcus erythropolis AJ270 microbial whole cell catalyst in neutral phosphate buffer at 30 °C, desymmetric hydrolysis of a series of prochiral 3-aryl and 3-arylmethylglutaramides efficiently afforded 3-substituted glutaric acid monoamides in up to 95% yield and >99.5% ee. Even far away from the reaction site, the substituents on the aryl still have a significant effect on the catalytic activity and enantioselectivity and different remote substituent effect was observed for the two types of substrates. The synthetic application of biocatalytic desymmetrization was demonstrated by the facile transformation of the obtained enantiopure (R)-3-substituted 4-carbamoylbutanoic acid products to chiral dihydroquinolinone and δ-lactone compounds. (Figure presented.).

PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 3-SUBSTITUTED GLUTARIC ACID MONOAMIDE

The process for producing an optically active 3-substituted glutaric acid monoamide is characterized in comprising the step of precipitating the optically active 3-substituted glutaric acid monoamide by mixing an acid and a mixed liquid containing an optically active 3-substituted glutaric acid monoamide represented by the following formula (2): wherein * indicates an asymmetric carbon atom; R1 is a C1-8 alkyl group, a C2-8 alkenyl group, a C2-8 alkynyl group, a C4-20 aryl group or a C5-20 aralkyl group; and the alkyl group, the alkenyl group, the alkynyl group, the aryl group and the aralkyl group may have a substituent, a basic compound, water and an organic solvent.

Chemoenzymatic enantioselective synthesis of baclofen

We report two different chemoenzymatic enantioselective syntheses of baclofen based on the distinction between enantiotopic ester groups in compounds bearing a prochiral centre. In the first approach, the key step is the highly stereoselective enzymatic hydrolysis of dimethyl 3-(4-chlorophenyl)glutarate by chymotrypsin in an aqueous medium. In the second approach, the key step is the enzyme-catalyzed esterification of 2-(4-chlorophenyl)-1,3-propanediol by acetic anhydride in the presence of a lipase in an organic medium. We report two different chemoenzymatic enantioselective syntheses of baclofen based on the distinction between enantiotopic ester groups in compounds bearing a prochiral centre. In the first approach, the key step is the highly stereoselective enzymatic hydrolysis of dimethyl 3-(4-chlorophenyl)glutarate by chymotrypsin in an aqueous medium. In the second approach, the key step is the enzyme-catalyzed esterification of 2-(4-chlorophenyl)-1,3-propanediol by acetic anhydride in the presence of a lipase in an organic medium.