Novel process for the preparation of (2r)-2-deoxy-2-fluoro-2-methyl-d-erythro-pentono-gamma-lactone and (2s)-2-deoxy-2-fluoro-2-methyl-d-erythro-pentono-gamma-lactone

A method for preparing compound 5 of the formula:

• which comprises:
• (a) adding a catalytic amount of a hypernucleophilic acylation catalyst to 2-fluoropropionic acid and 2-benzoxazolinone in a non-reactive solvent;
• and
• (b) adding a dehydrating agent to the mixture in step (a) with stirring;
• and
• (c) filtering the mixture in step (b) and concentrating the filtrate to provide compound 5.

A method for preparing a mixture of compounds of the formula 11 and 12:

• which comprises:
• (a) admixing a non-nucleophilic base and 1-(2-fluoro-1-oxopropyl)pyrrolidine in a non-reactive solvent;
• (b) admixing D-glyceraldehyde, 1,2-acetonide to the mixture from step (a);
• (c) neutralizing the mixture from step (b) and partitioning the resulting mixture between a volatile organic solvent and water and concentrating the volatile organic solution to provide an intermediate;
• (d) hydrolyzing the intermediate from step (c);
• and
• (e) concentrating the mixture from step (d) to provide a residue and partitioning the residue between water and a volatile organic solvent and concentrating the water phase to provide a residue, which is a mixture of 11 and 12.

A method for preparing a mixture of compounds of the formula 11 and 12:

• which comprises:
• (a) admixing a non-nucleophilic base and S-phenyl-2-fluoropropanethioate in a non-reactive solvent;
• (b) admixing D-glyceraldehyde, 1,2-acetonide to the mixture from step (a);
• (c) neutralizing the mixture from step (b) and partitioning the resulting mixture between a volatile organic solvent and water and concentrating the volatile organic solution to provide an intermediate;
• (d) hydrolyzing the intermediate from step (c);
• and
• (e) concentrating the mixture from step (d) to provide a residue and partitioning the residue between water and a volatile organic solvent and concentrating the water phase to provide a residue, which is a mixture of 11 and 12.

A method for preparing a mixture of compounds of the formula 11 and 12:

• which comprises:
• (a) admixing a non-nucleophilic base, S-phenyl-2-fluoropropanethioate, and chlorotriisopropoxytitanium (IV) in a non-reactive solvent;
• (b) admixing D-glyceraldehyde, 1,2-acetonide to the mixture from step (a);
• (c) neutralizing the mixture from step (b) and partitioning the resulting mixture between a volatile organic solvent and water and concentrating the volatile organic solution to provide an intermediate;
• (d) hydrolyzing the intermediate from step (c);
• and
• (e) concentrating the mixture from step (d) to provide a residue and partitioning the residue between water and a volatile organic solvent and concentrating the water phase to provide a residue, which is a mixture of 11 and 12.

A method for preparing a mixture of compounds of the formula 11 and 12:

• which comprises:
• (a) admixing 3-(2-fluoro-1-oxopropyl)-2(3H)-benzoxazolone to a non-reactive solvent;
• (b) admixing titanium (IV) chloride and a tertiary amine base to the mixture from step (a);
• (c) admixing D-glyceraldehyde, 1,2-acetonide to the mixture from step (b);
• (d) neutralizing the mixture from step (c) and partitioning the resulting mixture between a volatile organic solvent and water and concentrating the volatile organic solution to provide an intermediate;
• (e) hydrolyzing the intermediate from step (d);
• and
• (f) concentrating the mixture from step (e) to provide a residue and partitioning the residue between water and a volatile organic solvent and concentrating the water phase to provide a residue, which is a mixture of 11 and 12.