[Synthesis]
General procedure for the synthesis of 3-fluoro-4-(3-morpholinopropoxy)benzeneboronic acid from 4-(3-(4-bromo-2-fluorophenoxy)propyl)morpholine: a solution of 4-[3-(4-bromo-2-fluorophenoxy)-propyl]-morpholine (5.08 g, 15.96 mmol) in THF (10 mL) was added slowly and dropwise to a stirred magnesium slurry (582 mg, 1.5 equiv) in a mixture of THF (2 mL) and a small iodine crystal. After the dropwise addition was completed, the reaction mixture was heated to 90°C and maintained for 1 hour. Subsequently, the gray mixture was cooled to -78°C, trimethyl borate (1.2 eq., 2.15 mL) was added dropwise, and the mixture was allowed to warm slowly to room temperature overnight. After the reaction was complete, 2N HCl aqueous solution (60 mL) was added and stirred for 30 minutes, then extracted with ether (2 x 50 mL). Triethylamine was added to the aqueous layer, followed by extraction with ethyl acetate and ether. All organic phases were combined, dried and concentrated to give a brown oily product (3.8 g, 84% yield). The resulting product was used for subsequent reactions without further purification.1H NMR (D6-DMSO) δ 8.08 (2H, br s), 7.55 (1H, t, J = 8.75 Hz), 7.15 (2H, m), 4.04 (2H, t, J = 6.25 Hz), 3.57 (4H, m), 2.37 (6H, m), 1.84 (2H, m). ). LC-MS: rt 1.95 min, m/z 284 ES+. |