Process for making fluoroleucine ethyl esters
View Patent ↗The instant invention describes a novel reaction that includes spontaneous racemization of an azalactone via enol tautomerization. This racemization results in improved yield and ee over other reactions previously described.
1. A process for preparing a compound of formula I:
wherein R 1 is halo and R 2 is C 1-4 alkyl;
comprising an enzyme mediated ring opening of an azalactone of formula II: which process is a continuous plug flow column reaction
2. The process of claim 1 wherein wherein R 1 is fluoro and R 2 is ethyl.
3. The process of claim 2 wherein the enzyme is Candida antarctica lipase B, Pseudomonas fluorescens lipase, Pseudomonas cepacia lipase, cholesterol esterase, Porcine pancreas lipase, pancreatin, Candida antarctica lipase A, T. lanuginosa, Porcine liver lipase, P. stutzeri lipase, Mucor miehei lipase.
4. The process of claim 3 wherein the enzyme is Candida antarctica lipase B.
5. The process of claim 1 wherein the continuous plug flow column is fed with a first solution comprising an azalactone of formula II and a second solution comprising and amine base and EtOH.
6. The process of claim 5 wherein the amine base is triethylamine.