N-BOC-cis-4-fluoro-L-proline

• α4β2 Receptor ligands bearing pyrrolidine nucleus.
• β-Amino pyrrolidine-2-carbonitrile derivatives as possible dipeptidyl peptidase IV (DPP4) inhibitors.

203866-16-4

203866-13-1

General procedure for the synthesis of (2S,4S)-4-fluoro-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid from N-tert-butoxycarbonyl-cis-4-fluoro-L-proline methyl ester: To a solution of N-tert-butoxycarbonyl-cis-4-fluoro-L-proline methyl ester (5.83 g, 23.58 mmol) in tetrahydrofuran (THF, 30 mL) was added, at 0 °C, lithium hydroxide (LiOH, 1.98 g) in aqueous solution (30 mL). The reaction mixture was stirred at room temperature for 2 h. The pH was subsequently adjusted to 5 with dilute hydrochloric acid (1 M). After evaporating THF under reduced pressure, the pH of the aqueous layer was adjusted to 2 with dilute hydrochloric acid (1 M) and extracted with ethyl acetate (EtOAc, 80 mL x 3). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to afford (2S,4S)-4-fluoro-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid as a white solid (5.3 g, 96% yield). The structure of the compound was confirmed by the following spectral data: mass spectrum (ESI, positive ion mode) m/z: 234.24 [M + H]+; NMR hydrogen spectrum (400 MHz, CDCl3) δ (ppm): 8.76 (broad single peak, 1H), 5.28-5.12 (multiple peaks, 1H), 4.56-4.44 (multiple peaks, 1H), 3.86- 3.58 (multiple peaks, 2H), 2.77-2.01 (multiple peaks, 2H), 1.48-1.44 (double peaks, 9H, J = 16 Hz).