Synthesis
3-(2,3-dimethoxyphenyl)propionic acid (4.99 g, 23.7 mmol) was mixed with Eaton's reagent (47.5 mL, 3 g/mmol of raw material) and stirred at room temperature for 72 hours. Upon completion of the reaction, the mixture was slowly poured into ice water, neutralized to neutral, and subsequently extracted with ethyl acetate (3 x 75 mL). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by fast column chromatography using a pre-packed 100 g silica gel column [eluent A: ethyl acetate; eluent B: n-hexane; gradient elution: 7% A/93% B (1 column volume), 7% A/93% B→60% A/40% B (10 column volumes), 60% A/40% B (2 column volumes); flow rate: 40 mL/min; detection wavelengths: 254 nm and 280 nm] to give 4,5-dimethoxy-1-indanone (2.01 g, 10.5 mmol, 44% yield) as a yellow solid.1H NMR (CDCl3, 600 MHz) δ 7.06 (1H, d, J = 8.4 Hz), 6.62 (1H, d, J = 8.4 Hz), 3.61 (3H, s), 3.57 (3H, s), 2.70 (2.70 (2.70), 2.70 (2.70), 2.70 (2.70), 2.70 (3H, s), 2.70 (3H, s). s), 2.70 (2H, t, J = 5.4 Hz), 2.25 (2H, t, J = 5.4 Hz).13C NMR (CDCl3, 150 MHz) δ 204.6, 157.1, 147.4, 145.0, 130.7, 119.4, 112.0, 59.8, 55.8, 36.0, 22.1.
References
[1] Canadian Journal of Chemistry, 1982, vol. 60, # 21, p. 2678 - 2686
[2] Synthetic Communications, 2001, vol. 31, # 13, p. 2029 - 2036
[3] Journal of Medicinal Chemistry, 2011, vol. 54, # 9, p. 3331 - 3347
[4] Journal of Medicinal Chemistry, 1987, vol. 30, # 8, p. 1303 - 1308
[5] Journal of Organic Chemistry, 1984, vol. 49, # 12, p. 2130 - 2135
