Isopropanol → 3,5-Dimethoxy-a-(3-methoxyphenyl)benzenemethanol

Participants

Reaction Steps

A solution of 1-bromo-3-methoxybenzene (2.48 g, 13.24 mmol) in anhydrous THF (10 ml) was cooled to −78° C., evacuated and refilled with nitrogen for ten cycles. To this clear solution was slowly added n-butyl lithium (5.30 ml, 13.24 mmol) and stirred for 30 min. Then a solution of 3,5-dimethoxybenzaldehyde (2.00 g, 12.04 mmol) in anhydrous THF (10 ml) was added via a syringe. The mixture was stirred at −78° C. under nitrogen for 4 h then quenched with 2-propanol (2.1 ml, 27 mmol) and stirred overnight. To the orange colored mixture was added 30 ml of water and extracted with ether (3×60 ml). The combined ether extracts was washed with water (2×60 ml), dried over MgSO4, filtered and concentrated in vacuo to an oil, which was purified via flash column chromatography to give (3,5-dimethoxy-phenyl)-(3-methoxy-phenyl)-methanol as an off-white oil (2.69 g, 82%), HPLC purity was 98.3% at 2.81 min. (50/50 ACN/0.1% H3PO4): 1HNMR (CDCl3) δ 7.26-7.29 (m, 1H, Ar), 6.95-6.92 (m, 2H, Ar), 6.81-6.77 (m, 1H, Ar), 6.53 (d, J=2 Hz, 2H, Ar), 6.34 (t, J=2 Hz, 1H), 5.68 (d, J=3 Hz, 1H, CH), 3.77 (s, 3H, single OCH3 group), 3.74 (s, 6H, 2OCH3 groups), 2.45 (d, J=3 Hz, 1H, OH). The product was carried over to the next step.

Provenance & Evidence