GENERAL STEPS: (2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acid (2 g, 8.57 mmol), potassium carbonate (5.9 g, 42.69 mmol), and THF (80 mL) were mixed, and methyl iodide (6.1 g, 42.98 mmol) was added, and the reaction was stirred for 12 hours at room temperature. After completion of the reaction, the solid was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by rapid chromatography on silica gel with EtOAc/petroleum ether (1:5) as eluent to afford N-BOC-trans-4-fluoro-L-proline methyl ester (800 mg, 38% yield) as a colorless oil.
