Trifluoroacetic acid → HCID 67204571, compound

Temperature

90 °C

Cesium carbonate (806 mg, 2.48 mmol), Xantphos (95.0 mg, 0.165 mmol), and tris(dibenzylideneacetone)dipalladium (0) (76.0 mg, 0.082 mmol) were combined into vial fitted with a Teflon septum. The vial was flushed with argon and a solution of 2-(benzyloxy)-6-chloro-4-phenylpyridine (244 mg, 0.825 mmol) in 1,4-dioxane (2 ml) was added, followed by 2,4-dimethoxybenzylamine (0.249 ml 1.65 mmol). The solution was sparged with argon for 10 mins, then heated to 90° C. and stirred for 24 hours. The reaction mixture was cooled down to room temperature, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted two times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was dissolved in dichloromethane (2.5 mL), and trifluoroacetic acid (2.5 mL, 32.4 mmol) was added. After stirring at room temperature for 1 hour, the solvent was removed under reduced pressure. The residue was dissolved with ethyl acetate, and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted one time with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/ioshexane gradient) to give 6-(benzyloxy)-4-phenylpyridin-2-amine. LRMS (ESI) calculated for C18H17N2O [M+H]+, 277.1; found 277.0.

1. customThe vial was flushed with argon
2. customThe solution was sparged with argon for 10 mins
3. temperatureThe reaction mixture was cooled down to room temperature
4. additiondiluted with ethyl acetate
5. washwashed with saturated aqueous sodium bicarbonate
6. customThe organic layer was separated
7. extractionthe aqueous layer was back extracted two times with ethyl acetate
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe residue was dissolved in dichloromethane (2.5 mL)
12. stirringAfter stirring at room temperature for 1 hour
13. customthe solvent was removed under reduced pressure
14. dissolutionThe residue was dissolved with ethyl acetate
15. washwashed with saturated aqueous sodium bicarbonate
16. customThe organic layer was separated
17. extractionthe aqueous layer was back extracted one time with ethyl acetate
18. dry with materialThe combined organic layers were dried over sodium sulfate
19. filtrationfiltered
20. concentrationconcentrated
21. customThe residue was purified by column chromatography on silica gel (ethyl acetate/ioshexane gradient)

ORD record

ord-31fd9c8499f34f73a19de98c58725cea

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455477B2