Acetic Acid → HCID 28424096, compound

Temperature

70 °C

A mixture of aniline (2.26 g, 24.3 mmol), 2,6-difluorobenzaldehyde (3.79 g, 26.7 mmol) and glacial acetic acid (3.5 mL, 60.8 mmol) in dichloroethane (50 mL) was heated at 70° C. for 2 h. After cooling to rt, sodium triacetoxyborohydride (5.67 g, 26.8 mmol) was added and the mixture heated at 70° C. for 1.5 h, before cooling to rt, further sodium triacetoxyborohydride (5.67 g, 26.8 mmol) was added and the mixture was heated at 70° C. for a further 75 min before cooling to rt. H2O (50 mL), DCM (25 mL) and 1M aqueous NaOH (100 mL) were added and the phases were separated. The aqueous phase was extracted with DCM (2×50 mL) and the combined organic phases were extracted with DCM (2×50 mL), washed with brine (50 mL) and concentrated in vacuo. Purification by gradient column chromatography eluting with 0-20% EtOAc in heptane yielded the title compound (2.88 g, 13.1 mmol).

1. temperatureAfter cooling to rt
2. temperaturethe mixture heated at 70° C. for 1.5 h
3. temperaturebefore cooling to rt
4. temperaturethe mixture was heated at 70° C. for a further 75 min
5. temperaturebefore cooling to rt
6. customthe phases were separated
7. extractionThe aqueous phase was extracted with DCM (2×50 mL)
8. extractionthe combined organic phases were extracted with DCM (2×50 mL)
9. washwashed with brine (50 mL)
10. concentrationconcentrated in vacuo
11. customPurification by gradient column chromatography
12. washeluting with 0-20% EtOAc in heptane

ORD record

ord-467cd23cf5874b57b17d47f39eed287e

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249160B2