Hydrochloric Acid → HCID 118020716, compound

Temperature

-78 °C

To a solution of methoxymethyltriphenyl phosphonium chloride (5.4 g, 15.7 mmol) in THF (50 mL), n-butyl lithium (a 2.6 mol/L hexane solution, 6.3 mL, 16.5 mmol) was added under cooling at −78° C., and the resulting mixture was stirred for 30 minutes. The reaction mixture was heated to 0° C., a solution of 1-(5-fluoropyridin-2-yl)-1H-pyrazole-3-carbaldehyde obtained in Reference Example 29 (1.5 g, 7.9 mmol) and hexamethylphosphoric triamide (0.5 mL) in THF (50 mL) was added thereto, the resulting mixture was stirred for 3 hours, then heated to room temperature and stirred for 15 hours. To the reaction mixture, EtOAc and a saturated aqueous solution of sodium chloride were added under cooling in an ice bath and stirred to separate the organic layer. The organic layer was dried over MgSO4, then the drying agent was filtered off, and then the solvent was distilled off under reduced pressure to obtain a brown oil. To the obtained brown oil, an aqueous solution of hydrochloric acid (1.2 mol/L, 10 mL) was added, and the resulting mixture was heated to reflux and stirred for 2 hours. The reaction mixture was allowed to cool at room temperature, then water was added thereto, followed by extraction with EtOAc. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over MgSO4, then the drying agent was filtered off, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (HIP-Sil 25 g, hexane/EtOAc=80/20 to 20/80) to obtain the title compound (1.0 g) (light yellow oil).

1. temperatureThe reaction mixture was heated to 0° C.
2. additionwas added
3. stirringthe resulting mixture was stirred for 3 hours
4. temperatureheated to room temperature
5. stirringstirred for 15 hours
6. temperatureunder cooling in an ice bath
7. stirringstirred
8. customto separate the organic layer
9. dry with materialThe organic layer was dried over MgSO4
10. filtrationthe drying agent was filtered off
11. distillationthe solvent was distilled off under reduced pressure
12. customto obtain a brown oil
13. temperaturethe resulting mixture was heated
14. temperatureto reflux
15. stirringstirred for 2 hours
16. temperatureto cool at room temperature
17. extractionfollowed by extraction with EtOAc
18. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
19. dry with materialdried over MgSO4
20. filtrationthe drying agent was filtered off
21. distillationthe solvent was distilled off under reduced pressure
22. customThe obtained residue was purified by column chromatography (HIP-Sil 25 g, hexane/EtOAc=80/20 to 20/80)

ORD record

ord-867dfb1b991a4665b99940815733ef9d

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266870B2