2-O-benzyl 1-O-tert-butyl (2R,3S)-3-fluoropyrrolidine-1,2-dicarboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2R,3S)-3-fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (252 mg, 0.778 mmol; 72% purity by HPLC/215 nm) in MeOH (20 mL) was hydrogenated at RT (1 atm) over Pd/C 10% (35 mg, 10% w/w) for 24 h. The reaction mixture was filtered through a 0.45 microns filter and concentrated under reduced pressure to give the crude title compound (70% purity by HPLC/215 nm) as a white solid. This material was used in the next reaction step without further purification. MS (LC/MS): 232 [M−H]+; tR (HPLC conditions b): 2.78 min. was hydrogenated at RT for 24 h The reaction mixture was filtered through a 0.45 microns filter concentrated under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in a similar manner as described by J. A. Hodges et al., J. Amer. Chem. Soc. 2005, 127, 15923-15932: To a solution of (2S,3R)-3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (490 mg, 1.53 mmol) in CH2Cl2 (30 mL), cooled to −78° C., was added dropwise DAST (1.01 mL, 7.62 mmol). The reaction mixture was stirred at −78° C. for 5 h, and then was allowed to warm to RT and stirred overnight. After cooling to 0° C., the reaction was quenched with MeOH, followed by addition of aqueous NaHCO3 solution. Volatiles were removed under reduced pressure and the residue was taken up in EtOAc. The organics were washed with aqueous NaHCO3 (3×), water and brine, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:9) to give the title compound (89% purity by HPLC/215 nm). MS (LC/MS): 346 [M+Na]+, 268 [MH−tBu]+, 224 [MH−Boc]+; tR (HPLC conditions b): 5.31 min. The title compound was prepared in a similar manner to warm to RT stirred overnight After cooling to 0° C. the reaction was quenched with MeOH followed by addition of aqueous NaHCO3 solution Volatiles were removed under reduced pressure The organics were washed with aqueous NaHCO3 (3×), water and brine dried (Phase separator) concentrated in vacuo The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:9)