Hydrochloric Acid → 3-[5-Chloromethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde

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Reaction Steps

A mixture of 3-(5-hydroxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde (1.25 g, 3.41 mmol) (example 10c) and 12N HCl (8.5 mL) in toluene (35 mL) was heated at reflux for 1 hour. The solution was cooled to room temperature and the layers were separated. The aqueous layer was extracted twice with ethyl acetate. The organic combined extract was washed with water, brine, dried (MgSO4), filtered and evaporated. To the residue obtained (3-[5-chloromethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde) (example 10e), diluted in dimethylformamide (35 mL), were added potassium carbonate (3.49 g, 25.25 mmol) then dimethylamine hydrochloride (1.47 g, 18.04 mmol). The mixture was stirred at room temperature for 3 hours. Water was added and the layers separated. The mixture was extracted with ethyl acetate and the organic combined extract was washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was chromatographed on silica gel (10% methanol in dichloromethane) to afford 742 mg of 3-(5-Dimethylaminomethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde. 56% yield. 1H-NMR (300 MHz, CDCl3): 1.38 (s, 6H), 2.30 (s, 6H), 3.47 (s, 2H), 4.25 (s, 2H), 7.06 (s, 1H), 7.16 (s, 1H), 7.48 (d, J=8.5 Hz, 1H), 7.90 (dd, J1=8.5 Hz, J2=2.1 Hz, 1H), 8.03 (d, J=2.1 Hz, 1H), 10.03 (s, 1H).

Provenance & Evidence