Hydrochloric Acid → 6-Fluoro-2,3-dimethoxybenzaldehyde

Temperature

-78 °C

To a cold (−78° C.) solution of 4-fluoro-1,2-dimethoxybenzene (15.00 g, 96.05 mmol) in anhydrous THF (150 mL) was added n-BuLi (84.5 mL, 211.32 mmol, 2.5 M solution in hexanes) under nitrogen and stirred it for 3 h at −78° C. Quenched the reaction with DMF (75 mL) at −65° C., added 2N HCl (300 mL) dropwise and further stirred for 30 min. Two layers separation was observed. Aqueous layer was extracted with EtOAc. Combined organic layers were washed with water, brine and dried over MgSO4. Filtered the ethyl acetate layer and concentrated it in vacuo. The title compound was purified by flash column chromatography using pure hexanes then 10 and 20% EtOAc in hexanes which provided 14.40 g (78.19 mmol, 82%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.23 (s, 1H), 7.36 (dd, J=9.0, 5.1 Hz, 1H), 7.03 (t, J=9.6 Hz, 1H), 3.87 (s, 3H), 3.83 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ ppm −131.68-−131.66 (m, 1F).

1. customQuenched
2. customthe reaction with DMF (75 mL) at −65° C.
3. stirringfurther stirred for 30 min
4. customTwo layers separation
5. extractionAqueous layer was extracted with EtOAc
6. washCombined organic layers were washed with water, brine
7. dry with materialdried over MgSO4
8. filtrationFiltered the ethyl acetate layer
9. concentrationconcentrated it in vacuo
10. customThe title compound was purified by flash column chromatography

ORD record

ord-1c7531d48e384bcf9177804dac9db2fa

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703742B2