203380-45-4

Upstream product

• 66192-25-4 2-bromo-5-methoxybenzyl chloride 
• 150192-39-5 2-Bromo-5-methoxybenzyl alcohol 
• 203576-34-5 3-(2-bromo-5-methoxy-phenyl)-1-(2,2-dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-methyl-propan-1-one 
• 22921-68-2 2-bromo-5-methoxy-benzoic acid 
• 203380-43-2 (S)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid 

Downstream Products

• 203380-46-5 (2S)-3-(2-bromo-5-methoxyphenyl)-1-(tert-butyldimethylsiloxy)-2-methylpropane 
• 203380-38-5 3-{2-[3-(tert-butyl-dimethyl-silanyloxy)-2-methyl-propyl]-4-methoxy-phenyl}-3-(6-butyl-3-formyl-pyridin-2-yl)-propionic acid tert-butyl ester 
• 203380-43-2 (S)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid 

Relevant academic research and scientific papers

Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

A novel chromium trioxide catalyzed oxidation of primary alcohols to the carboxylic acids

A novel CrO3 catalyzed oxidation of primary alcohols to the carboxylic acids is reported. The oxidation proceeds smoothly with only 1-2 mol % of CrO3 and 2.5 equivalents of H3IO6 in wet MeCN to give the carboxylic acids in excellent yield. No significant racemization is observed for alcohols with adjacent chiral centers. Secondary alcohols are cleanly oxidized to ketones.