Triethylamine → (3-(4-(2-Oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

Participants

Reaction Steps

To a solution of 4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (70 mg, 0.20 mmol) in dichloromethane (2 mL) was added triethylamine (0.100 mL, 0.72 mmol) and 2-oxa-7-azaspiro[4.4]nonane hydrochloride (77 mg, 0.47 mmol). The resulting mixture was stirred for 30 minutes at ambient temperature, after which was added sodium triacetoxyhydroborate (114 mg, 0.54 mmol). Stirring was continued at ambient temperature overnight, after which NaHCO3 (aq, sat, 5 ml) was added to the reaction mixture. The phases were separated using a phase separator. The aqueous phase was extracted twice with dichloromethane and dried with the aid of a phase separator. The combined organic phases were concentrated in vacuo to afford a colourless residue weighing 112 mg. The crude material was purified by preparative reverse-phase HPLC at pH 10 to give 75 mg (81%) of the desired product as a solid. 1H NMR (600 MHz, CDCl3): δ 1.75 (t, 2H), 1.79-1.89 (m, 2H), 2.32 (d, 1H), 2.45-2.49 (m, 2H), 2.59 (dd, 1H), 3.43 (d, 1H), 3.48-3.56 (m, 3H), 3.63-3.75 (m, 2H), 4.10 (dd, 1H), 4.56 (dd, 1H), 4.61-4.67 (m, 1H), 5.10 (dd, 1H), 5.16 (ddd, 1H), 6.86 (d, 2H), 7.26 (d, 2H), 7.63-7.73 (m, 3H), 8.06-8.11 (m, 2H). MS (APCI+) m/z 461.2 [M+H]+, LC purity: 97%

Provenance & Evidence