Acetic Acid → 2-Bromo-6-fluorobenzaldehyde

Temperature

-78 °C

To a solution of diisopropylamine (15.7 ml 112 mmol) in anhydrous tetrahydrofuran (200 ml) cooled to 0° C. was added dropwise n-butyllithium (2.5M in hexanes, 44.8 ml, 112 mmol). After complete addition the mixture was cooled to −78° C. and 3-fluorobromobenzene (19.6 g, 112 mmol) added over 10 minutes. The mixture stirred at −78° C. for 1 hour then N,N diimethylformamide (9.72 ml, 125 mmol) was added dropwise over 5 minutes. The mixture was stirred for a further 10 minutes, then acetic acid (10 ml) and water (350 ml) were added. The mixture was allowed to warm to room temperature and was extracted with Et2O (250+150 ml). The combined extracts were washed with water (×2) 0.2N HCl, brine, dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica eluting with 5% Et2O in iso-hexanes to give the title compound (20 g, 88%) as a white solid.

1. additionAfter complete addition the mixture
2. additionN,N diimethylformamide (9.72 ml, 125 mmol) was added dropwise over 5 minutes
3. stirringThe mixture was stirred for a further 10 minutes
4. temperatureto warm to room temperature
5. extractionwas extracted with Et2O (250+150 ml)
6. washThe combined extracts were washed with water (×2) 0.2N HCl, brine
7. dry with materialdried over Na2SO4
8. customevaporated
9. customThe residue was purified by column chromatography on silica eluting with 5% Et2O in iso-hexanes

ORD record

ord-f47d9f97980746b585f719f113eaa8a1

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07285563B2