Tandem crystallization strategies for resolution of 3,3,3‐trifluorolactic acid [CF3CH(OH)COOH] by chiral benzylamines

• Published in: Chirality (New York, N.Y.) Vol. 31; no. 11; pp. 979 - 991
• Main Authors: Wong, Lawrence W.‐Y., Vashchenko, Elena V., Zhao, Ying, Sung, Herman H.‐Y., Vashchenko, Valerii V., Mikhailenko, Vadim, Krivoshey, Alexander I., Williams, Ian D.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2019
• Subjects: Acids; Contamination; Crystallization; Desiccants; diastereomeric salt formation; Enantiomers; Filtrate; Molecular sieves; Phenethylamine; Phenylethylamine; pyramidal disorder; Recrystallization; resolution; solid solutions; tandem crystallization; trifluorolactic acid; tandem crystallization; solid solutions; trifluorolactic acid; resolution; diastereomeric salt formation; pyramidal disorder
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23127

Resolution of rac‐3,3,3‐trifluorolactic acid by diastereomeric salt formation was reinvestigated. The use of (S)‐1‐phenylethylamine gives coprecipitation of two diastereomeric phases, 1 (S)‐[NH3CH(CH3)Ph](S)‐[CF3CH(OH)COO] and 2 (S)‐[NH3CH(CH3)Ph](R)‐[CF3CH(OH)COO]·H2O. Pure phase 1 may be obtained using molecular sieves as desiccants. Resolution by (S,S)‐2‐amino‐1‐phenylpropan‐1,3‐diol gives monoclinic (S,S)‐[NH3CH(CH2OH)CHOHPh] (R)‐[CF3CH(OH)‐COO] 3 with minor (S)‐3,3,3‐trifluorolactate contamination, which is precluded in the recrystallized orthorhombic form 4. A new resolution using inexpensive phenylglycinol gives pure phase 5 (S)‐[NH3CH(CH2OH)Ph] (S)‐[CF3CH(OH)COO] in 76% yield, 94% ee in a single step, in preference to its (S)‐(R) diastereomer 6. Overall efficient resolution for both enantiomers of the trifluorolactic acid (each ca. 70% yield, 99% ee) may be achieved by various two‐step “tandem” crystallizations, involving direct addition of either water or a second base to the filtrate from the initial reaction. Efficient resolution of 3,3,3‐trifluorolactic acid (each enantiomer ca. 70% yield and 99%ee) is achieved by two step "tandem" diastereomeric salt crystallizations, using bases such as 1‐phenylethylamine and phenylglycinol.