Diisopropylethylamine → Benzyl 4-(2-(3,3-difluoroazetidin-1-yl)-2-oxoethoxy)piperidine-1-carboxylate

Participants

Reaction Steps

2-(1-(Benzyloxycarbonyl)piperidin-4-yloxy)acetic acid (4.12 g, 14.05 mmol), 3,3-difluoroazetidine hydrochloride (1.4 g, 10.81 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (3.47 g, 10.81 mmol) were dissolved in DMF (50 mL), to this was added DIPEA (4.91 mL, 28.10 mmol) and the reaction was stirred overnight. The solvent was evaporated and the reaction mixture was quenched with 2M NaOH (50 mL), extracted with Et2O (3×50 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford the desired material as a yellow gum (2.59 g, 65.1% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.67-1.49 (2H, m), 1.90-1.81 (2H, m), 3.26-3.19 (2H, m), 3.58-3.51 (1H, m), 3.84-3.78 (2H, m), 4.13 (2H, s), 4.36 (2H, t), 4.60 (2H, t), 5.12 (2H, s), 7.40-7.29 (5H, m).

Provenance & Evidence