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Tandem crystallization strategies for resolution of 3,3,3‐trifluorolactic acid [CF 3 CH(OH)COOH] by chiral benzylamines
Author(s) -
Wong Lawrence W.Y.,
Vashchenko Elena V.,
Zhao Ying,
Sung Herman H.Y.,
Vashchenko Valerii V.,
Mikhailenko Vadim,
Krivoshey Alexander I.,
Williams Ian D.
Publication year - 2019
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.23127
Subject(s) - chemistry , diastereomer , yield (engineering) , monoclinic crystal system , orthorhombic crystal system , enantiomer , coprecipitation , enantiomeric excess , crystallization , medicinal chemistry , chiral resolution , resolution (logic) , stereochemistry , crystallography , inorganic chemistry , crystal structure , organic chemistry , catalysis , enantioselective synthesis , materials science , artificial intelligence , computer science , metallurgy
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)‐[NH 3 CH(CH 3 )Ph](S)‐[CF 3 CH(OH)COO] and 2 (S)‐[NH 3 CH(CH 3 )Ph](R)‐[CF 3 CH(OH)COO]·H 2 O. 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)‐[NH 3 CH(CH 2 OH)CHOHPh] (R)‐[CF 3 CH(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)‐[NH 3 CH(CH 2 OH)Ph] (S)‐[CF 3 CH(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.