HCID 21520350, compound → 2-Amino-2-hydroxy-3-fluoro-propionate

Participants

Reaction Steps

This reductive amination reaction is conveniently conducted by first equilibrating a salt of fluoropyruvic acid hydrate (e.g. lithium 2,2-dihydroxy-3-fluoro-propionate) in aqueous ammoniacal solution with formation of the corresponding salt of 2-amino-2-hydroxy-3-fluoro-propionic acid (e.g. lithium, sodium or ammonium 2-amino-2-hydroxy-3-fluoro-propionate) and the salt of 2,2-diamino-3-fluoro-propionate; the equilibrium ratio of 2,2-diamino-3-fluoro-propionate to 2-amino-2-hydroxy-3-fluoro-propionate thus formed is a function of ammonia concentration and, in concentrated aqueous ammonia (13 N), the ratio is approximately 95 to 5. Although not ordinarily preferred, lower aqueous ammonia concentrations may be used; for example with 6.5 N aqueous ammonium hydroxide, the equilibrium ratio is approximately 90 to 10. Upon reduction, this mixture would necessarily result in a reduced yield of 3-fluoro-DL-alanine and an increased amount of 3-fluoro-lactate by-product. The equilibration at 37° C. is a pseudo-first-order reaction with a half-life of 15 minutes; equilibration at 37° C. for 90 minutes provides six half-lives, and an effective ratio of 2,2-diamino-3-fluoropropionate to 2-amino-2-hydroxy-3-fluoro-propionate of 95 to 5. Although the 2,2-diamino-3-fluoropropionate salt is not isolated from the ammonia solution, its presence, in a purity of 95%, is readily demonstrated by NMR (nuclear magnetic resonance) measurement.

Provenance & Evidence