Development of Practical and Scalable Synthetic Route for 1-(2,2,2-Trifluoroethyl)cyclopropane-1-carboxylic Acid
An efficient, scalable, and safe synthesis of 1-(2,2,2-trifluoroethyl)cyclopropane-1-carboxylic acid (compound 1) was developed, starting from the inexpensive and readily available trifluoro-iodopropane 18. This was accomplished through detailed optimization of the conditions for the key Simmons–Smith cyclopropanation reaction. The optimized process was used to prepare multi-kilograms of this intermediate, supporting early development activities of a pharmaceutical candidate.
Authors
- Rajaram Ayothiraman
- Ian Hale
- Martin D. Eastgate (ORCID: https://orcid.org/0000-0002-6487-3121)
- Francisco González‐Bobes (ORCID: https://orcid.org/0000-0001-7876-7154)
- Arundutt Silamkoti
- Zulelal Dolas
- Alla Venu
- Jeishla L. M. Matos
- Sukhen Karmakar (ORCID: https://orcid.org/0000-0003-3699-6367)
- Thirumalai Lakshminarasimhan
- Arvind Mathur (ORCID: https://orcid.org/0000-0002-7702-4006)
- Anuradha Gupta
- Arvind Venkataramani
- Sundar Nandhagopal
- Sabuj Mukherjee
- Srinivasarao Jami
Institutions
- Bristol-Myers Squibb (Germany) (DE)
- Discovery Centre (CA)
- Bristol-Myers Squibb (United States) (US)
- Université Bourgogne Franche-Comté (FR)
- Bristol-Myers Squibb (United Kingdom) (GB)
- Bristol-Myers Squibb (India) (IN)
- Biocon (India) (IN)
- Syngene International (India) (IN)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2026-01-05
- DOI
- https://doi.org/10.1021/acs.oprd.5c00371
- Primary Topic
- Cyclopropane Reaction Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00