Hydrochloric Acid → HCID 86638082, compound

Temperature

-20 °C

Isopropylmagnesium chloride-lithium chloride complex (1M, 21.46 mL, 21.46 mmol) was added to 2-bromo-1-(difluoromethyl)-4-fluorobenzene (4.39 g, 19.51 mmol) in THF (120 mL) cooled to −20° C. under nitrogen. The resulting solution was stirred at −20° C. for 1 hour. N,N-Dimethylformamide (1.813 mL, 23.41 mmol) was added, and the mixture stirred for a further 1 hour, maintaining the temperature in the range −15 to −20° C. The mixture was allowed to warm to ambient temperature, then 2M hydrochloric acid (100 mL) was added and the mixture was extracted with EtOAc (150 mL). The organic layer was washed with saturated sodium bicarbonate (120 mL) and concentrated to yield crude product. The crude product was purified by flash silica chromatography, elution gradient 5 to 10% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 2-(difluoromethyl)-5-fluorobenzaldehyde (1.250 g, 36.8%) as a colourless liquid.

1. stirringthe mixture stirred for a further 1 hour
2. temperaturemaintaining the temperature in the range −15 to −20° C
3. temperatureto warm to ambient temperature
4. extractionthe mixture was extracted with EtOAc (150 mL)
5. washThe organic layer was washed with saturated sodium bicarbonate (120 mL)
6. concentrationconcentrated
7. customto yield crude product
8. customThe crude product was purified by flash silica chromatography, elution gradient 5 to 10% EtOAc in isohexane
9. customPure fractions were evaporated to dryness

ORD record

ord-c4c0123c9fe349c48afc17d3fbe30016

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258140B2