442682-41-9

Upstream product

• 442682-38-4 bis[(isobutyryloxy)methyl] 4-[2-(difluoromethoxy)phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate 
• 442682-35-1 bis(2-cyanoethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate 
• 442682-36-2 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid 
• 71653-64-0 o-difluoromethoxybenzaldehyde 
• 442682-40-8 (-)-(4R)-4-[2-(difluoromethoxy)phenyl]-5-{[(isobutyryloxy)methoxy]carbonyl}-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid 
• 74-88-4 methyl iodide 
• 400884-08-4 3-[(isobutyryloxy)methyl] 5-methyl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate 

Downstream Products

• 400884-19-7 (-)-(4S)-4-[2-(difluoromethoxy)phenyl]-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid 

Relevant academic research and scientific papers

Effect of acyl chain length and branching on the enantioselectivity of Candida rugosa lipase in the kinetic resolution of 4-(2-difluoromethoxyphenyl)-substituted 1,4-dihydropyridine 3,5-diesters

Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)-pheny]l-2,6-dimethyl-1,4-dihydro-3, 5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3- [(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3, 5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.

An efficient chemoenzymatic approach to enantiomerically pure 4-[2-(difluoromethoxy)phenyl] substituted 1,4-dihydropyridine-3,5-dicarboxylates

An efficient chemoenzymatic synthesis of (-)-3-methyl 5-(2-propoxyethyl) (4R)-4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3, 5-pyridinedicarboxylate has been achieved. The key step is a highly stereoselective Candida rugosa lipase (CRL)-mediate