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

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of 93 (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 (91a).

Provenance & Evidence