General procedure for the synthesis of (S)-4,4-difluoropyrrolidine-2-carboxylic acid methyl ester hydrochloride from N-BOC-4,4-difluoro-L-proline methyl ester: N-BOC-4,4-difluoro-L-proline methyl ester (3 g, 11.3 mmol) was mixed with EtOAc solution (15 mL) of 4 M HCl and the reaction was stirred at room temperature for 4 hours. After completion of the reaction, the mixture was concentrated in vacuum to afford methyl (S)-4,4-difluoropyrrolidine-2-carboxylate hydrochloride (2.27 g, 100% yield) as a white solid. The structure of the compound was confirmed by the following spectral data: MS-ESI: m/z 166.14 [M + H]+; 1H NMR (400 MHz, CDCl3): δ 4.70-4.69 (m, 1H), 3.75-3.87 (m, 2H), 3.71 (s, 3H), 2.91-3.00 (m, 1H), 2.70-2.81 (m, 1H).
