Chemical Properties
colorless to light yellow liquid
Uses
3,5-Bis(trifluoromethyl)benzonitrile is a pharmaceutical intermediate compound used in the preparation of Selinexor, a selective nuclear output inhibitor approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and multiple myeloma.
Synthesis
To a 2L three-necked flask was added 300 g (1.17 mol) of 3,5-bis(trifluoromethyl)benzamide, 183.6 g (0.7 mol) of triphenylphosphine, 107.7 g (0.7 mol) of carbon tetrachloride and 400 ml of tetrahydrofuran. The reaction mixture was heated to 60°C under stirring and maintained for 180 minutes. Upon completion of the reaction, 6 g (0.04 mol) of phosphorus pentoxide was added, followed by a distillation device in a flask and distillation at atmospheric pressure to collect the 155°C fraction, yielding 237.1 g of product. Gas chromatographic analysis showed the fraction to be 3,5-bis(trifluoromethyl)benzonitrile in a yield of 0.99 mol with a target yield of 99.8% (yield: 85%). Examples 17-31 Various (fluoroalkyl)benzene derivatives were prepared according to the same method as in Examples 2-16. In order to improve the purity of the product, Example 17 underwent two crystallization operations and the final distillation step was repeated in the remaining Examples. （The purity, residual halogen content and residual metal content of the (fluoroalkyl)benzene derivatives are summarized in Table 2.
References
[1] Patent: EP1500641, 2005, A1. Location in patent: Page 11
[2] Synthesis (Germany), 2015, vol. 47, # 23, p. 3758 - 3766
