Aluminium lithium hydride → 3-Amino-3-(3-fluoro-4-(trifluoromethyl)phenyl)propan-1-ol

Temperature

0 °C

To a stirred suspension of 274 (2.0 g, 8.0 mmol) and THF (25 mL) under N2 at 0:C was added dropwise 1M LiAlH4 in THF (12 mL, 12 mmol) and the reaction stirred at 0° C. in an ice bath for 1.5 h. The cold reaction mixture was quenched by carefully adding the reaction mixture to a satd. solution of Rochelle's salt (50 mL) that was cooled in an ice bath and adequately vented. The resulting mixture was stirred for 18 h while warming to RT slowly as the ice bath melted. The mixture was diluted with EtOAc (50 mL) and filtered through CELITE to remove solids which were rinsed several times with EtOAc. The phases were separated and the aqueous phase re-extracted with EtOAc (30 mL). The combined organic extracts were washed with brine (50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with 5% 7N NH3 in MeOH in DCM (500 mL to pre-wash column, followed by 500 mL of eluent, then 500 mL of 7.5% 7N NH3 in MeOH in DCM) to afford 0.43 g (22%) of 3-amino-3-(3-fluoro-4-(trifluoromethyl)phenyl)propan-1-ol (276).

1. customThe cold reaction mixture
2. customwas quenched
3. additionby carefully adding the reaction mixture to a satd
4. temperaturesolution of Rochelle's salt (50 mL) that was cooled in an ice bath
5. stirringThe resulting mixture was stirred for 18 h
6. temperaturewhile warming to RT slowly as the ice bath
7. additionThe mixture was diluted with EtOAc (50 mL)
8. filtrationfiltered through CELITE
9. customto remove solids which
10. washwere rinsed several times with EtOAc
11. customThe phases were separated
12. extractionthe aqueous phase re-extracted with EtOAc (30 mL)
13. washThe combined organic extracts were washed with brine (50 mL)
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe crude product was purified by SiO2 chromatography
18. washeluting with 5% 7N NH3 in MeOH in DCM (500 mL
19. washto pre-wash column

ORD record

ord-415533d70a374b0a9caf797c1fc115ee

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133187B2