1-(2-Methoxy-5-methylphenyl)ethanone

Preparation

Preparation by reaction of acetic acid with 4-methylanisole in the presence of trifluoromethyl-sulfonic anhydride (Tf2O) for 3 min at r.t. (97%).

Synthesis

General procedure for the synthesis of 1-(2-methoxy-5-methylphenyl)ethanone from p-toluene methyl ether and acetyl chloride: 1. An ethanolic solution of acetyl chloride (6.79 mL, 95.1 mmol) was slowly added dropwise to a 50 mL suspension in dichloromethane containing aluminum chloride (12.69 g, 95.1 mmol) at 0 °C. 2. Subsequently, a solution of 1-methoxy-4-methylbenzene (intermediate LXXXVII) (9.69 g, 79.4 mmol) in 50 mL of dichloromethane was slowly added dropwise to the above reaction mixture.3. After the dropwise addition was completed, the reaction mixture was stirred at room temperature for 3 h. 4. Upon completion of the reaction, the reaction was quenched with 1.5 N hydrochloric acid solution and the reaction mixture was extracted with dichloromethane.5. The organic extract was combined and washed sequentially with water and The organic extracts were combined, washed sequentially with water and brine, and then dried over anhydrous sodium sulfate.6 After evaporation of the solvent, the crude product was purified by column chromatography (silica gel 100-200 mesh, eluent ratio 15:85 ethyl acetate:hexane) to afford 1-(2-methoxy-5-methylphenyl)ethanone in 69% yield.7 The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.528 (s, 1H), 7.247 (bs, 1H), 6.852-6.873 (d, 1H, J = 8.4 Hz), 3.881 (s, 3H), 2.601 (s, 3H), 2.299 (s, 3H).

References

[1] Patent: WO2012/90219, 2012, A2. Location in patent: Page/Page column 86
[2] Chemische Berichte, 1928, vol. 61, p. 1999
[3] Vikram, 1959, vol. 3, # 1, p. 1,3