A practical procedure for the large-scale preparation of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate, a key intermediate for diltiazem.

doi:10.1021/JO025647B

Paper

A practical procedure for the large-scale preparation of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate, a key intermediate for diltiazem.

Published May 21, 2002 · T. Furutani, Ritsuo Imashiro, M. Hatsuda

The Journal of organic chemistry

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26

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Abstract

A practical synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), was developed. Treatment of methyl (E)-4-methoxycinnamate 3 with chiral dioxirane, generated from chiral ketone 4, provided (-)-2 in 77% ee and 89% yield. The crude mixture of (-)-2 and 4 was efficiently separated by the use of novel and simple equipment performing a lipase-catalyzed transesterification and a continuous dissolution and crystallization to furnish the optically pure (-)-2 and recovery of 4 in 74% and 91% yield, respectively.

Study Snapshot

This study developed a practical method for large-scale preparation of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem, using novel and simple equipment.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Paper

A practical procedure for the large-scale preparation of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate, a key intermediate for diltiazem.

References

Citations

Development of Organocatalytic Darzens Reactions Exploiting the Cyclopropenimine Superbase

Cyclopropenimine superbases provide a highly organocatalytic approach to the Darzens reaction, yielding,-epoxy carbonyl compounds in good yields.

Asymmetric reduction of 2-chloro-3-oxo-ester into enantiomerically high pure diltiazem precursor by a Candida ketoreductase

Candida ketoreductase effectively asymmetrically reduces 2-chloro-3-oxo-ester into enantiomerically high pure diltiazem precursor, offering an eco-friendly and cost-effective route for industrial synthesis of diltiazem.

Epoxide Syntheses and Ring-Opening Reactions in Drug Development

Epoxide chemistry has been successfully used in the synthesis of high-profile pharmaceuticals, including diltiazem, reboxetine, and carfilzomib, for various indications and molecular scaffolds.

Microbial lipases and their industrial applications: a comprehensive review

Microbial lipases have diverse industrial applications, with potential for increased market profitability and reduced environmental liability through immobilization techniques and carrier types.

Asymmetric catalysis in synthetic strategies for chiral benzothiazepines

Asymmetric catalysis, including metal, organocatalysis, and enzymatic catalysis, enables efficient and diverse synthesis of chiral benzothiazepines, benefiting pharmaceutical research.

Recent Advances in Iminium-Salt-Catalysed Asymmetric Epoxidation

Iminium-salt-catalyzed asymmetric epoxidation has advanced to provide up to 98% enantioselectivity in kinetic resolution of racemic chromenes and 73% enantioselectivity for nitrogen-protected dihydroquinoline

Asymmetric Epoxidation in Stereoselective Synthesis

Asymmetric epoxidation methods are crucial for the stereoselective synthesis of biologically interesting compounds, including drug substances and natural products.