Hydrochloric Acid → Methyl 3-(4-{[4-(methyloxy)phenyl]carbonyl}phenyl)propanoate

Participants

Reaction Steps

4-[3-(Methyloxy)-3-oxopropyl]benzoic acid (66) (1.0 g, 4.80 mmol) was dissolved in CH2Cl2 (25 mL). Oxalyl chloride (0.86 mL, 9.61 mmol) was added dropwise, followed by addition of two drops of DMF. The reaction mixture was stirred at room temperature for 2 h. Methylene chloride and the excess of oxalyl chloride were removed under vacuum. The residue was dissolved in CH2Cl2 (15 mL) with anisole (1.05 mL, 9.60 mmol). Cooled in an ice bath, AlCl3 (0.97 g, 7.20 mmol) was added in portions. The mixture was stirred at 0° C. for 3.5 h, then stirred at room temperature for 1.5 h. Poured into 1 N HCl (25 mL) with ice, the mixture was extracted with CH2Cl2 (3×50 mL). The combined CH2Cl2 extract was washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give brown oil. The crude product was purified by chromatography on a silica gel column eluted with hexanes:EtOAc (8:1 to 5:1) to give 0.90 g (63%) of the title compound 167 as cotton-like white solid. 1H NMR (400 MHz, CDCl3): δ 2.68 (t, J=7.7 Hz, 2H), 3.03 (t, J=7.7 Hz, 2H), 3.68 (s, 3H), 3.89 (s, 3H), 6.96 (d, J=8.8 Hz, 2H), 7.30 (d, J=8.1 Hz, 2H), 7.70 (d, J=8.1 Hz, 2H), 7.81 (d, J=8.8 Hz, 2H)+. LCMS (ESI): m/z 299 (M+H)+.

Provenance & Evidence