152397-94-9

Upstream product

• 152397-85-8 methyl 2,2-dichloro-3-(4-methoxyphenyl)-3-oxopropionate 
• 123-11-5 4-methoxy-benzaldehyde 
• 199783-35-2 (2,2-dichloro-1-methoxy-vinyloxy)-trimethysilane 
• 22027-50-5 methyl 3-(4-methoxybenzoyl)acetate 
• 78437-40-8 methyl 2-chloro-3-(4-methoxyphenyl)-3-oxopropionate 
• 100-06-1 1-(4-methoxyphenyl)ethanone 

Downstream Products

• 336113-23-6 (S)-2-Chloro-3-hydroxy-3-(4-methoxy-phenyl)-propionic acid methyl ester 
• 105560-93-8 methyl (2R,3S)-3-(4-methoxyphenyl)glycidate 

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.

Asymmetric synthesis of methyl (2R,3S)-3-(4-methoxyphenyl) glycidate, a key intermediate of diltiazem, via Mukaiyama aldol reaction

Methyl (2R,3S)-3-(4-methoxyphenyl) glycidate, a key intermediate of diltiazem, was synthesized in good yield with high enantioselectivity based on chiral oxazaborolidine-mediated Mukaiyama aldol reaction of p-anisaldehyde with α,α-dichloro silyl ketene acetal (up to 96% ee), followed by reduction and cyclization.

Asymmetric reduction of aromatic ketones. II. An enantioselective synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate

Asymmetric reduction of some 3-keto esters (6, 8, and 11) to 3-hydroxy esters (7, 9, and 12) with various chiral reducing agents was investigated. The products (9 and 12) were converted to methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (2R,3S-3), a key intermediate in the practical enantioselective synthesis of diltiazem (1).