Isopropanol → (2,3-Dihydrobenzo[1,4]dioxin-6-yl)-(3,5-dimethoxyphenyl)methanol

A solution of 6-bromo-2,3-dihydrobenzo[1,4]dioxine (1.09 g, 5.07 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 (2.03 ml, 5.07 mmol) and stirred for 30 min. Then a solution of 3,5-dimethoxybenzaldehyde (0.77 g, 4.61 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 (2.10 ml, 27.65 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 (10% EtOAc in hexane gradient to 40% EtOAc in hexane in about 40 min.) to give (2,3-dihydro-benzo[1,4]dioxin-6-yl)-(3,5-dimethoxy-phenyl)-methanol as a light brown oil (1.27 g, 91%), HPLC purity was 93.4% at 3.45 min. (50/50 ACN/0.1% H3PO4): 1HNMR (CDCl3) δ 6.88-6.79 (m, 3H, Ar), 6.54 (d, J=2 Hz, 2H, Ar), 6.35 (t, J=2 Hz, 1H, Ar), 5.65 (d, J=3 Hz, 1H, CH), 4.22 (m, 4H, 2CH2), 3.77 (s, 6H, OCH3), 2.25 (d, J=3 Hz, 1H, OH). The product was carried over to the next step.

1. customevacuated
2. additionrefilled with nitrogen for ten cycles
3. stirringThe mixture was stirred at −78° C. under nitrogen for 4 h
4. stirringstirred overnight
5. extractionextracted with ether (3×60 ml)
6. washThe combined ether extracts was washed with water (2×60 ml)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo to an oil, which
10. customwas purified via flash column chromatography (10% EtOAc in hexane gradient to 40% EtOAc in hexane in about 40 min.)

ORD record

ord-d359795617864ed4a29ba4a79843d1da

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07312241B2