Process for preparing nateglinide and intermediates thereof
The process of reacting trans-4-isopropylcyclohexane carboxylic acid with thionyl chloride in the presence of an organic amide and subsequent conversion addresses contamination issues in nateglinide production, achieving high purity and yield by minimizing cis isomer presence and improving the trans isomer ratio.
Patent Information
- Application Number
- PCT/US2003/021238
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2003-06-16
- Filing Date
- 2003-07-03
- Publication Date
- 2004-01-15
AI Technical Summary
Current processes for preparing nateglinide often result in contamination with the undesirable cis isomer and contamination with minor amounts of the methyl ester, leading to suboptimal yields and purity of the therapeutically effective trans isomer.
A process involving the reaction of trans-4-isopropylcyclohexane carboxylic acid with thionyl chloride in the presence of a C1 to C6 organic amide to obtain trans-4-isopropylcyclohexane acid chloride substantially free of the cis isomer, followed by conversion to nateglinide, using a two-phase system or an aqueous solution with a neat reagent, to enhance purity and yield.
The process achieves nateglinide production with a purity of at least 95% and minimal detection of the cis isomer, reducing contamination and improving the ratio of the therapeutically effective trans isomer, thereby enhancing the quality and yield of the final product.