Dimethylformamide → 6-Bromo-2-fluoro-3-methoxybenzaldehyde

Temperature

0 °C

To a solution of diisopropylamine (11 mL) in anhydrous THF (50 mL) was cooled to 0° C. and was added 1.6 M n-butyl lithium/hexanes (47 mL) dropwise under nitrogen atmosphere. The mixture was stirred for 10 min at 0° C. and was then cooled to −78° C. with an acetone dry ice bath. A solution of 4-bromo-2-fluoro-1-methoxybenzene (7.9 mL, 61 mmol) in anhydrous THF (50 mL) was added dropwise. The mixture was then allowed to stir for 30 min at −78° C. DMF (7.5 mL) was added dropwise at −78° C. The reaction was stirred for 1 h at room temperature. Half of the solvent from the solution was removed under reduced pressure and the solution was extracted using ethyl acetate, water (300 mL), and 1 M HCl (65 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was crystallized by washing with hexanes. The solid was collected by filtration and dried under reduced pressure to give 6-bromo-2-fluoro-3-methoxybenzaldehyde (8.21 g, 58%).

1. temperaturewas then cooled to −78° C. with an acetone dry ice bath
2. stirringto stir for 30 min at −78° C
3. stirringThe reaction was stirred for 1 h at room temperature
4. customHalf of the solvent from the solution was removed under reduced pressure
5. extractionthe solution was extracted
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. customThe solvent was removed under reduced pressure
10. customThe residue was crystallized
11. washby washing with hexanes
12. filtrationThe solid was collected by filtration
13. customdried under reduced pressure

ORD record

ord-ac1d30887ef141059ef28b77e01a6da5

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145429B2