Dimethylformamide → 4-Bromo-2,6-difluorobenzaldehyde

To a solution of diisopropylamine (93 mL, 0.66 mol) in dry tetrahydrofuran (300 mL) at −50° C. was added n-BuLi (212 mL of 2.M in hexanes, 0.53 moL) dropwise. The solution was stirred at room temperature for 30 mins. This solution was then added dropwise to a cooled (−75° C.) solution of 1-bromo-3,5-difluorobenzene (84 g, 0.44 mol) in dry tetrahydrofuran (900 mL). The mixture was stirred at −78° C. for one hour. Dry dimethylformamide (63.6 mL, 0.82 mol) was added and the mixture was stirred for two hours. The cooling bath was removed and the mixture was slowly warmed to room temperature. The mixture was diluted with diethyl ether and poured into cooled 1 M aqueous hydrochloric acid (1 L). The aqueous phase was extracted with diethyl ether. The combined phases were dried, filtered, and the solvent was removed in vacuo to give the crude product. The crude was re-crystallized with ethyl acetate and petroleum ether to afford the title compound.

1. additionThis solution was then added dropwise to
2. stirringThe mixture was stirred at −78° C. for one hour
3. stirringthe mixture was stirred for two hours
4. customThe cooling bath was removed
5. temperaturethe mixture was slowly warmed to room temperature
6. additionThe mixture was diluted with diethyl ether
7. additionpoured
8. temperatureinto cooled 1 M aqueous hydrochloric acid (1 L)
9. extractionThe aqueous phase was extracted with diethyl ether
10. customThe combined phases were dried
11. filtrationfiltered
12. customthe solvent was removed in vacuo
13. customto give the crude product
14. customThe crude was re-crystallized with ethyl acetate and petroleum ether

ORD record

ord-2f905f5a3700439f8709b690f1358560

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420695B2