Isopropanol → Benzo[1,3]dioxol-5-yl-(3-ethoxy-4-methoxy-phenyl)-methanol

Temperature

-78 °C

A stirred mixture of 4-bromo-2-ethoxy-1-methoxy-benzene (1.65 g, 7.1 mmol) and dry THF (15 mL) was cooled to −78° C., evacuated and refilled with nitrogen for 10 cycles. To this clear solution was slowly added n-butyllithium (2.9 mL, 7.1 mmol) and stirred for 20 min. Then a mixture of benzo[1,3]dioxole-5-carbaldehyde (0.98 g, 6.5 mmol) in dry THF (20 mL) was added and stirred for 1 hour at −78° C. The mixture was quenched with isopropanol (3.0 mL, 39 mmol) and added water (10 mL). The mixture was extracted with EtOAc (3×50 mL). The combined organic phases were washed with water (2×50 mL), dried over MgSO4 and concentrated to oil, which was purified by flash column chromatography (EtOAc/Hexane) to give benzo[1,3]dioxol-5-yl-(3-ethoxy-4-methoxy-phenyl)-methanol as an off-white solid (1.1 g, 56% yield): 1H NMR (CDCl3) δ 1.44 (t, J=7 Hz, 3H, CH2CH3), 2.11 (d, J=3 Hz, 1H, OH), 3.86 (s, 3H, OCH3), 4.07 (q, J=7 Hz, 2H, CH2CH3), 5.71 (d, J=3 Hz, 1H, CH), 5.93 (s, 2H, CH2), 6.74-6.91 (m, 6H, Ar). The product was used in the next step without further purification.

1. customevacuated
2. additionrefilled with nitrogen for 10 cycles
3. additionwas added
4. stirringstirred for 1 hour at −78° C
5. extractionThe mixture was extracted with EtOAc (3×50 mL)
6. washThe combined organic phases were washed with water (2×50 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated to oil, which
9. customwas purified by flash column chromatography (EtOAc/Hexane)

ORD record

ord-7b02fff4fec647268baae68e986b7eed

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470723B2