Cesium carbonate → HCID 66917287, compound

Temperature

100 °C

A toluene solution (20 ml) of benzophenone imine (2.38 g, 13.1 mmol), tris(dibenzylidene acetone)dipalladium (275 mg, 0.3 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (XANTPHOS) (347 mg, 0.6 mmol) and cesium carbonate (5.83 g, 17.9 mmol) were added to a toluene solution (60 ml) of 1-bromo-4,5-difluoro-2-propoxybenzene (3.0 g, 11.9 mmol). The mixture was stirred under a nitrogen atmosphere at 100° C. for 23 hours. After the reaction mixture was cooled to room temperature, water and a saturated ammonium chloride aqueous solution were added. The resulting mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was dissolved with diethyl ether (60 ml), and concentrated hydrochloric acid (10 ml) was added to the resulting solution, which was then stirred for 2 hours. A 5N sodium hydroxide aqueous solution (24 ml) was added to the reaction mixture to get a pH=11, and concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with a saturated sodium chloride aqueous solution. The organic layer was concentrated under reduced pressure. The residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=9:1). The purified product was concentrated under reduced pressure to thereby obtain 850 mg of oily dark brown 4,5-difluoro-2-propoxyaniline (yield: 38%).

1. temperatureAfter the reaction mixture was cooled to room temperature
2. extractionThe resulting mixture was extracted with ethyl acetate
3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved with diethyl ether (60 ml), and concentrated hydrochloric acid (10 ml)
6. additionwas added to the resulting solution, which
7. stirringwas then stirred for 2 hours
8. additionA 5N sodium hydroxide aqueous solution (24 ml) was added to the reaction mixture
9. customto get a pH=11
10. concentrationconcentrated under reduced pressure
11. dissolutionThe residue was dissolved in dichloromethane
12. washwashed with a saturated sodium chloride aqueous solution
13. concentrationThe organic layer was concentrated under reduced pressure
14. customThe residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=9:1)
15. concentrationThe purified product was concentrated under reduced pressure

ORD record

ord-fd0fc189091a454b8a3f1a597573abc4

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642619B2