Dimethylformamide → 6-Bromo-2,4-difluoro-3-methoxybenzaldehyde

Temperature

0 °C

Add n-butyl lithium 1.6N (22 ml, 35.2 mmol) to diisopropylamine (4.8 ml, 34.2 mmol) in anhydrous THF (7 ml) at 0° C. Stir the resulting yellow solution for 30 min at 0° C. Add this LDA solution dropwise via canula to a solution of 5-bromo-1,3-difluoro-2-methoxybenzene (5.83 g, 26.17 mmol) in anhydrous THF (40 ml) at −78° C. over 40 min. Stir the resulting bright yellow solution for 50 min at −78° C. Add anhydrous DMF (2.7 ml, 34.8 mmol) and stir the mixture for 1.5 h at −78° C. Quench the mixture with dilute sulfuric acid and extract the product with EtOAc (×3). Wash the combined organic layers with water (×3), saturated aq. sodium chloride and dry over anhydrous sodium sulfate. Filter and concentrate to yield the crude product. Purification by flash chromatography (Silica gel-hexane/EtOAc) yields the title compound.

1. stirringStir the resulting bright yellow solution for 50 min at −78° C
2. customQuench the mixture with dilute sulfuric acid
3. extractionextract the product with EtOAc (×3)
4. washWash the combined organic layers with water (×3), saturated aq. sodium chloride
5. dry with materialdry over anhydrous sodium sulfate
6. filtrationFilter
7. concentrationconcentrate
8. customto yield the crude product
9. customPurification by flash chromatography (Silica gel-hexane/EtOAc)

ORD record

ord-7fc61f9df81040f2be821a7b4c31d756

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07393868B2