Flurbiprofen → HCID 21405819, compound

To a chilled (0° C.) solution of 2-(2-fluoro-biphenyl-4-yl)propionic acid in THF was added isobutyl chloroformate followed by dropwise addition of TEA. The resulting white slurry was allowed to stir for 1 hour and then diluted with THF (50 mL) and filtered. The filter cake was washed with additional THF (50 mL) and the filtrate was concentrated to approximately 50 mL using a rotary evaporator. The concentrated filtrate was then stirred at −20° C. and a solution of NaBH4 in H2O (20 mL) was dropwise added over a period of 15 minutes. The resulting suspension was stirred for 2 hours at 0° C., diluted with water (200 mL), and extracted with ethyl acetate (2×100 mL). The ethyl acetate layers were combined and washed with 1.0 N HCl solution (100 mL) followed by a 5% bicarbonate solution wash (100 mL). The ethyl acetate solution was then concentrated to an oily residue of 2-(2-fluoro-biphenyl-4-yl)propanol (4.47 g, 95% yield).

1. additionfollowed by dropwise addition of TEA
2. filtrationfiltered
3. washThe filter cake was washed with additional THF (50 mL)
4. concentrationthe filtrate was concentrated to approximately 50 mL
5. customa rotary evaporator
6. stirringThe concentrated filtrate was then stirred at −20° C.
7. additiona solution of NaBH4 in H2O (20 mL) was dropwise added over a period of 15 minutes
8. stirringThe resulting suspension was stirred for 2 hours at 0° C.
9. additiondiluted with water (200 mL)
10. extractionextracted with ethyl acetate (2×100 mL)
11. washwashed with 1.0 N HCl solution (100 mL)
12. washwash (100 mL)

ORD record

ord-3719f8e1da9c4394872e1be9e263d8c3

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212155B2