Tetrahydrofuran → 6-Fluoro-2,3-dimethoxybenzaldehyde

To a solution of 4-fluoro-1,2-dimethoxy-benzene (20.0 g, 128.07 mmol) in anhydrous THF (200 mL) under nitrogen at −78° C. was added dropwise a 2.5M solution in hexane of n-BuLi (102.4 mL, 256.14 mmol) for duration 30 min and the reaction mixture was further stirred at the same temperature for 3 h. The reaction mixture was quenched carefully with DMF (100 mL) at −65° C. to −40° C. and left overnight. 2N HCl (300 mL) was added dropwise at −60° C. and the mixture stirred for 30 min. The two layers were separated and the aqueous layer extracted with EtOAc. The combined organic layers were washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. Purification was completed by flash column chromatography (20% EtOAc/hexane). Yield 18.0 g (85%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.39 (s, 1H), 7.09 (dd, J=9.4, 5.1 Hz, 1H), 6.84 (t, J=9.6 Hz, 1H), 3.98 (s, 3H), 3.88 (s, 3H). 19F NMR (376 MHz, CHLOROFORM-d): −126 ppm.

1. customThe reaction mixture was quenched carefully with DMF (100 mL) at −65° C. to −40° C.
2. waitleft overnight
3. addition2N HCl (300 mL) was added dropwise at −60° C.
4. stirringthe mixture stirred for 30 min
5. customThe two layers were separated
6. extractionthe aqueous layer extracted with EtOAc
7. washThe combined organic layers were washed with water and brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customPurification

ORD record

ord-707e58b1b9c44bb0836161291ff70e26

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703742B2