Triethylamine → 7-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

Participants

Reaction Steps

Under argon, hydroxylamine hydrochloride (514 mg, 7.40 mmol) and sodium acetate (607 mg, 7.4 mmol) were initially charged in abs. methanol (15 ml), and after 5 minutes of stirring at room temperature, a solution of 6-methoxy-1-indanone (1000 mg, 6.17 mmol) in abs. methanol (10 ml) was added. The resulting reaction mixture was stirred at room temperature for 3 h. After removal of the solvent under reduced pressure, the residue was taken up in dichloromethane, and water was added. The aqueous phase was extracted repeatedly with dichloromethane and the combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Without further purification, the resulting 6-methoxyindan-1-one oxime (1000 mg, 5.64 mmol) was dissolved in dichloromethane (15 ml), triethylamine (1.02 ml, 7.34 mmol) was added and the mixture was stirred under argon at room temperature for 20 min. After cooling to 0° C., methanesulphonyl chloride (840 mg, 7.34 mmol) was added. The reaction mixture obtained in this manner was stirred at room temperature for 4 h, and water was then added. After repeat extraction of the aqueous phase with dichloromethane, the combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Without any further purification, the 6-methoxyindan-1-one methanesulphonyloxime (1000 mg, 3.92 mmol) that remained was dissolved in dichloroethane (3 ml) under argon, and boron trifluoride etherate complex (0.50 ml, 3.95 mmol), methanesulphonyl chloride (0.50 ml, 6.46 mmol) and titanium tetrachloride (0.50 ml, 4.56 mmol) were added, in each case dropwise. Under argon, the resulting reaction solution was stirred at room temperature for 6 h and then cooled to 0° C., and water and saturated sodium bicarbonate solution were added carefully. After repeated thorough extraction of the aqueous phase with dichloromethane, the combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification of the residue that remained by column chromatography (gradient ethyl acetate/n-heptane) gave 7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (380 mg, 55% of theory) in the form of a colourless solid. 1H-NMR (400 MHz, CDCl3 δ, ppm) 7.59 (d, 1H), 7.12 (d, 1H), 7.00 (dd, 1H), 6.30 (br. s, 1H, NH), 3.83 (s, 3H), 3.54 (m, 2H), 2.93 (m, 2H).

Provenance & Evidence