Ethyl Acetate → 2-(1-Bromoethyl)3-(4-fluorophenyl)-3H-quinazolin-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 7.084 g 2-ethyl-3-(4-fluorophenyl)-3H-quinazoline-4-one (IV) (26.40 mmol, 1.000 equiv) and 2.60 g sodium acetate (31.7 mmol, 1.20 equiv) dissolved in 30 mL glacial acetic acid at 40° C. (external temperature; oil bath) was added dropwise by addition funnel a solution of 1.36 mL bromine (26.4 mmol, 1.00 equiv) in 5 mL glacial acetic acid over 60 min. Upon completed addition of the bromine solution, the reaction was stirred an additional 60 min, after which time TLC indicated no IV remained (Rf=0.44; 40% ethyl acetate in hexane) and the heterogeneous mixture was poured into 400 mL water. The resulting aqueous, acidic mixture, with precipitate, was stirred vigorously at ambient temperature for two h. The precipitate was collected by vacuum filtration, rinsing with warm (ca. 40° C.) water (2×50 mL) and cold isopropyl alcohol (50 mL). The solid was dried in vacuo over phosphorous pentoxide overnight, affording 8.81 g of a white solid.m.p. 179.8° C. 1H NMR (CDCl3) δ2.06 (d, J=0.016p, 3H), 4.55 (q, 0.016p, 2H), 7.16 (ddd, 1H, J1=2.4 Hz, J2=4.8 Hz, J3=8.4 Hz), 7.24 (dt, 1H, J1=2.8 Hz, J2=8.0 Hz), 7.28 (dt, 1H, J1=2.8 Hz, J2=8.4 Hz), 7.51-7.58 (m, 2H), 7.80-7.81 (m, 2H), 8.28 (dt, 1H, J1=0.8 Hz, J2=8.0 Hz) ppm. MS (ESI+) 348.0 [MH]+.

Provenance & Evidence