Process for preparing fluoroleucine alkyl esters

1. A processes for preparing a compound of formula IA:

comprising the steps of:

a. alkylating an imine carboxylate of formula IIA with methallyl halide to form a substituted imine of formula IIIA;

b. deprotecting the substituted imine of formula IIIA with an acid to yield an amine of formula IVA;

c. resolving the amine of formula IVA with a chiral protic acid selected from the group consisting of D-(+)-camphor-10-sulfonic acid, D-BOC-proline, di-p-tolyl-D-tartaric acid, N-acetyl-D-phenyl alanine and mixtures thereof, in the presence of 5-nitrosalicylaldehyde;

d. fluorinating the resolved amine to yield the compound of formula IA;

wherein X is H 2 SO 4 , L-tartaric acid, D-BOC proline, L-(−)-10-camphorsulfonic acid or N-acetyl-D-phenyl alanine.

2. The process of claim 1 , wherein step a. is performed in the presence of a strong base.

3. The process of claim 2 , wherein the strong base is selected from the group consisting of potassium t-butoxide, lithium t-butoxide, sodium t-butoxide, LDA, sodium hydride, n-BuLi, sec-BuLi, t-BuLi, LiHMDS, NaHMDS, KHMDS, LiTMP and mixtures thereof.

4. The process of claim 1 , wherein step a. is performed in the presence of a polar aprotic solvent.

5. The process of claim 1 , wherein the acid is selected from the group consisting of hydrochloric acid, triflic acid, sulfuric acid, p-toluenesulfonic acid, naphthalene disilfonic acid, trifluoroacetic acid and mixtures thereof.

6. The process of claim 1 , wherein step d. is performed with a fluorinating agent selected from the group consisting of Olah's reagent, HF-pyridine, HF-triethylamine, HF-Urea, HF-melamine, HF and mixtures thereof.

7. The process of claim 6 wherein the fluorinating agent is Olah's reagent.

8. The process of claim 1 , wherein the chiral protic acid is D-(+)-camphor-10-sulfonic acid.

9. A compound of formula IA.

wherein X is L-Tartaric acid, D-BOC proline, L-(−)-10-camphorsulfonic acid or N-acetyl-D-phenyl alanine.

10. A compound of formula