Industrial Consultancy & Sponsored Research (IC&SR) , IIT Madras
Processes for Preparing Chiral 3,3-Disubstituted Oxindoles
Categories for this Invention
Categories: Drugs & Pharmaceutical Engineering | Chemistry & Chemical Analysis
Industry: Chemical Synthesis
Application: Pharmaceutical Synthesis
Market: The Chiral Chemical market size was valued at USD 58.82 Billion in 2021 and is predicted to reach USD 150 Billion by 2030 with a CAGR of 9.8% from 2022-2030.
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Problem Statement
- Traditional methods for chiral 3,3-disubstituted oxindole synthesis are harsh and limited in scope, hindering pharmaceutical applications.
- Diazo compounds, commonly used precursors, pose safety risks due to instability, limiting their practical use. Few successful methods exist for capturing chiral Csp3-Pd intermediates, crucial for efficient synthesis.
- Hence, a one-step, enantioselective synthesis method for chiral 3,3-disubstituted oxindoles from versatile starting materials is needed to overcome above mentioned limitations and meet pharmaceutical demands.
Technology
The instant invention introduces a novel method combining transition metal catalysis with enantioselective reactions, driving advancements in synthetic chemistry.
A process for preparing a compound of formula (III) the process comprising: reacting a compound of formula (I) with compound of formula (II) wherein ‘R’ and ‘R1’ are independently selected from a group comprising hydrogen, alkyl group, alkoxy group and halo group; wherein the ligand is (R)-DTBM SEGPHOS (compound of formula V).
- The reaction is conducted in a solvent system comprising dimethylformamide (DMF), dichloromethane (DCM), dichloroethane (DCE), and a co-solvent system DCE:H2O, with a 1:1 ratio of 1,2-dichloroethane and dimethylformamide.
- Optimal reaction conditions involve a temperature range of 70°C to 90°C for 24 hours.
- Following the reaction, isolation and purification steps, including solvent addition, quenching, filtration, extraction, and column chromatography, are performed to obtain desired product.
Key Features / Value Proposition
- Guarantees the production of optically pure chiral compounds crucial for pharma use.
- Utilizes safer N-tosyl hydrazones instead of hazardous diazo compounds, expanding substrate options & enhancing safety in Lab.
- Incorporates a precise combination of palladium catalyst, ligand, base, and silver salt additives to ensure high yields and selectivity.
- Provides specific parameters for temperature, reaction time, and reagent concentrations, enabling reproducibility and scalability.
- Simplifies the synthetic pathway with a one-step process, saving time and resources.
- Facilitates the synthesis of valuable chiral building blocks for drug development.
- Offers cost-effective approach using accessible starting materials.
Questions about this Technology?
Contact For Licensing
sm-marketing@imail.iitm.ac.in
ipoffice2@iitm.ac.in
Research Lab
Prof. Govindasamy Sekar
Department of Chemistry
Intellectual Property
IITM IDF No.: 2445
IP No.: 463317 (Granted)
Technology Readiness Level
TRL-3
Proof of Concept