Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov;31(11):979-991.
doi: 10.1002/chir.23127. Epub 2019 Sep 30.

Tandem crystallization strategies for resolution of 3,3,3-trifluorolactic acid [CF3 CH(OH)COOH] by chiral benzylamines

Lawrence W-Y Wong  1 , Elena V Vashchenko  1   2 , Ying Zhao  1 , Herman H-Y Sung  1 , Valerii V Vashchenko  1   2 , Vadim Mikhailenko  2 , Alexander I Krivoshey  2 , Ian D Williams  1
Affiliations

Tandem crystallization strategies for resolution of 3,3,3-trifluorolactic acid [CF3 CH(OH)COOH] by chiral benzylamines

Lawrence W-Y Wong et al. Chirality. 2019 Nov.

Abstract

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)-[NH3 CH(CH3 )Ph](S)-[CF3 CH(OH)COO] and 2 (S)-[NH3 CH(CH3 )Ph](R)-[CF3 CH(OH)COO]·H2 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)-[NH3 CH(CH2 OH)CHOHPh] (R)-[CF3 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)-[NH3 CH(CH2 OH)Ph] (S)-[CF3 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.

Keywords: diastereomeric salt formation; pyramidal disorder; resolution; solid solutions; tandem crystallization; trifluorolactic acid.

PubMed Disclaimer

References

REFERENCES

    1. Kubota T, Kondo Y, Oyama T, Tanaka T. Synthesis and reactions of 2-alkoxy-1,1,3,3,3-pentafluoropropenes as a synthon for trifluoromethylated compounds. Nippon Kagaku Kaishi. 1989;21(9):1576-1586.
    1. Takahashi S, Jukurogi T, Katagiri T, Uneyama K. Isomorphic supramolecular structures via one-dimensional hydrogen bonding motifs in crystals of chiral difluorolactates, trichlorolactates and trifluorolactates. CrystEngComm. 2006;8(4):320-326.
    1. Katagiri T, Uneyama K. Chiral recognition by multicenter single proton hydrogen bonding of trifluorolactates. Chem Lett. 2001;30(12):1330-1331.
    1. Kubota T, Kanega J, Katagiri T. Application of (S)-trifluorolactic acid for chiral derivatizing agent. J Fluorine Chem. 1999;97(1-2):213-221.
    1. Ramachandran PV, Gong B, Brown HC. Chiral synthesis via organoboranes. 40. A simple one-pot synthesis of the enantiomers of (trifluoromethyl) oxirane. A general synthesis in high optical purities of a-trifluoromethyl secondary alcohols via the ring cleavage reactions of the epoxide. J. Org. Chem. 1995;60(1):41-46.

Publication types

LinkOut - more resources