Acetic Acid → 2-Chloro-6-fluoro-N-phenylbenzenemethanamine

Temperature

70 °C

A mixture of aniline (3.95 mL, 43.3 mmol), 2-fluoro-6-chlorobenzaldehyde (7.46 g, 47.7 mmol) and glacial acetic acid (6.2 mL, 105.2 mmol) in dichloroethane (100 mL) was heated at 70° C. for 2 h. After cooling to rt, sodium triacetoxyborohydride (13.8 g, 65.1 mmol) was added and the mixture stirred at rt for 2.5 h, before further sodium triacetoxyborohydride (4.6 g, 21.7 mmol) was added and the mixture stirred at rt for 1 h. H2O (100 mL) was added cautiously and the mixture was stirred for 5 min; 10M aqueous NaOH (20 mL) and DCM (50 mL) were added, the phases were separated, and the aqueous phase was extracted with DCM (2×50 mL). The combined organic phases were washed with brine (50 mL) and concentrated in vacuo. Purification by gradient column chromatography eluting with 0-10% EtOAc in iso-hexane yielded the title compound (10.5 g, 44.6 mmol).

1. temperatureAfter cooling to rt
2. additionwas added
3. stirringthe mixture was stirred for 5 min
4. customthe phases were separated
5. extractionthe aqueous phase was extracted with DCM (2×50 mL)
6. washThe combined organic phases were washed with brine (50 mL)
7. concentrationconcentrated in vacuo
8. customPurification by gradient column chromatography
9. washeluting with 0-10% EtOAc in iso-hexane

ORD record

ord-ed1d81615c8d46af83a031a465032e08

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249160B2