137173-39-8

Upstream product

• 78437-40-8 methyl 2-chloro-3-(4-methoxyphenyl)-3-oxopropionate 
• 123-11-5 4-methoxy-benzaldehyde 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 22027-50-5 methyl 3-(4-methoxybenzoyl)acetate 

Relevant academic research and scientific papers

Highly enantioselective Mukaiyama aldol reaction of αα-dichloro ketene silyl acetal: An efficient synthesis of a key intermediate for diltiazem

An efficient synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), has been developed on the basis of the highly enantioselective Mukaiyama aldol reaction of p-anisaldehyde (4a) with αα-dichloro ketene silyl acetal 5. Thus, the reaction using a stoichiometric amount of chiral oxazaborolidinone catalyst 12a proceeded to excellent yield (83%) and high enantioselectivity (96% ee), together with the chiral ligand 13a in nearly quantitative recovery. The reaction using a substoichiometric amount of 12e (20 mol%) also proceeded to excellent yield (88%), with somewhat lower enantioselectivity (77% ee). The aldol product 3a thus obtained was easily converted to (-)-2 in excellent yield (80%) and high optical purity (>99% ee). The highly enantioselective Mukaiyama aldol reaction with 5 catalyzed by 12a proved to be applicable to various aldehydes. An efficient preparation of 5 from inexpensive starting materials was also described.

Stereoselective Synthesis of Diltiazem via Dynamic Kinetic Resolution

An efficient synthesis of diltiazem has been developed using dynamic kinetic resolution (DKR) as a key step. The methyl (2S,3S)-2-chloro-3-hydroxy-3- (4-methoxyphenyl)propionate was synthesized from a racemic mixture of α-chloro-β-keto ester, with high anti diastereoselectivity (92%) and enantioselectivity (95%), based on an asymmetric hydrogenation reaction with a chiral ruthenium(II) catalyst, simply prepared by mixing Ru(cod)(2-methylallyl) 2 with the atropisomeric ligand (S)-MeO-BIPHEP. By treatment of this α-chloro-β-hydroxy ester with a base, the corresponding trans methyl glycidate, a key intermediate of diltiazem, was easily obtained.

A new enantioselective synthesis of glycidates via dynamic kinetic resolution of racemic 2-chloro-3-keto esters using chiral Ru (II) complexes

2-chloro-3-keto esters were quantitatively hydrogenated to syn and anti 2-chloro-3-hydroxyester by asymmetric hydrogenation with chiral ruthenium (II) catalysts prepared in-situ from (COD)Ru(2-methylallyl)2 in presence of atropisomeric ligands such as MeO-Biphep and Binap, giving enantioselectivity up to 99%, 2-chloro-3-hydroxy esters were treated with different bases to give (E)-and (Z)-2,3-epoxyalkanoates in 65-90% yields with 84-97% ee.