Sodium Cyanide → (3-(4-((4-(Hydroxymethyl)-4-methylpiperidin-1-yl)methyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

Participants

Reaction Steps

To a solution of 69C (1.65 g, 5.42 mmol) in methanol (25 mL) was added commercially available ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate (1.30 g, 5.96 mmol) followed by sodium cyanide (53 mg, 1.10 mmol). The reaction mixture was stirred at RT overnight. The solvent was removed by evaporation and the residue was dissolved in DCM. The solution was washed with NaHCO3, filtered through a phase separator and then evaporated to near dryness. Ether was added and the formed solid was filtered off and washed with ether. The product was dried in vacuo to afford 1.85 g (72%) of 69 as a crystalline solid, m. p. 167° C. 1H NMR (500 MHz, CDCl3): δ 0.96 (s, 3H), 1.31 (m, 2H), 1.52 (m, 2H) 2.28 (m, 2H), 2.34 (s, 3H), 2.51 (m, 2H), 3.38 (s, 2H), 3.40 (s, 2H), 4.31 (dd, 1H), 4.62 (dd, 1H), 4.73 (dd, 1H), 5.05 (m, 1H), 5.13 (m, 1H), 6.54 (dd, 1H), 6.60 (d, 1H), 7.18 (d, 1H), 7.53 (t, 2H), 7.59 (t, 1H), 8.17 (d, 2H), MS (APCI+) m/z 477 [M+H]+, LC purity: 99%.

Provenance & Evidence