2-Fluoro-3-methylbutanoic acid → 1-Phenethylamine

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Reaction Steps

The 2-fluoro-3-methylbutyric acid (˜235.5 g, 1.96 mol), is taken up in ethyl acetate (2.9 L) and R-(+)-α-methylbenzylamine (237.5 g, 1.96 mol) is added dropwise via an addition funnel. A temperature rise to 40° C. is observed. Upon allowing the solution to cool, a slurry results and is stirred at room temperature for 45 minutes. The slurry is then filtered and the filter cake rinsed with ethyl acetate (300 mL). The wet cake is suspended in ethyl acetate (4.5 L) and heated to reflux. Additional ethyl acetate (450 mL) is added to provide a solution, and then the solution is allowed to stand at room temperature overnight. The resulting slurry is filtered and the filter cake rinsed with ethyl acetate (200 mL). The filter cake is vacuum dried at 40° C. to afford 262.3 g of the (R)-+-α-methylbenzylamine salt of (S)-2-fluoro-3-methylbutyric acid as a powder. The enantiomeric excess of this salt is found to be >94% by chiral capillary electrophoresis analysis for the desired (S) isomer.

Provenance & Evidence