Triethylamine → HCID 71225876, compound

Participants

Reaction Steps

Oxa-5-azaspiro[3.4]octane TFA salt (0.111 g, ca. 70%, 0.34 mmol) and 3-methoxy-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.13 g, 0.34 mmol) were mixed in dichloromethane (2 ml). Triethylamine (0.1 ml, 0.72 mol) was then added, followed by sodium triacetoxyhydroborate (0.145 g, 0.69 mmol). The mixture was stirred at ambient temperature overnight. LC-MS showed some remaining starting material. An additional amount of sodium triacetoxyhydroborate (0.1 g) was added and stirring was continued for 6 hours. The reaction mixture was then diluted with dichloromethane (10 ml) and shaken with NaHCO3 (sat. 3 ml). The two phases were separated by the use of a phase separator. Evaporation of the organic phase afforded a residue, which was purified by preparative reverse-phase HPLC at pH 10 to give 0.107 g of the desired product as a solid. The obtained product was further purified by automated flash chromatography on a 10 g column. 3% of NH3 (2M) in MeOH/EtOAc was used as the mobile phase. The product was detected by a UV detector at 274 nm. After evaporation of the solvent mixture was obtained 0.09 g (55%) of the desired product as a solid. 1H NMR (400 MHz, CDCl3) δ 1.71 (dt, 2H), 2.18-2.24 (m, 2H), 2.60 (t, 2H), 3.89 (s, 3H), 3.97 (s, 2H), 4.39-4.47 (m, 1H), 4.57 (d, 2H), 4.63 (dd, 1H), 4.83 (t, 1H), 4.90 (d, 2H), 5.03-5.15 (m, 2H), 6.63 (d, 1H), 6.87 (d, 1H), 6.95 (s, 1H), 7.5-7.62 (m, 3H), 8.17 (d, 2H). MS (APCI+) m/z 477.3 [M+H]+, LC purity: 97%.

Provenance & Evidence