Diethyl Ether → (βS)-β-Amino-4-fluoro-α,α-dimethylbenzeneethanol

Participants

Reaction Steps

A solution of (S)-methyl 2-amino-2-(4-fluorophenyl)acetate (0.500 g, 2.73 mmol) in diethyl ether (2.0 mL) was added dropwise to a 0° C. solution of methylmagnesium bromide (3.0 M in diethyl ether) (commercially available from Sigma-Aldrich, Milwaukee, Wis., 5.46 mL, 16.38 mmol). The ice bath was then removed, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was cooled to 0° C., diluted with EtOAc, and quenched by the addition of saturated aqueous ammonium chloride solution. The solution was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The aqueous phase was separated and extracted with EtOAc. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford a yellow-brown oil. The residual oil was dissolved in DCM and passed through a Silycycle SCX column washing with MeOH and then with 7 N ammonia in MeOH. The ammonia solution was concentrated to afford (S)-1-amino-1-(4-fluorophenyl)-2-methylpropan-2-ol (0.365 g, 1.992 mmol, 73% yield) as a yellow-brown oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.94 (s, 3H), 1.00 (s, 3H), 1.99 (s, 2H), 3.69 (s, 1H), 4.38 (s, 1H), 7.07 (t, J=8.95 Hz, 2H), 7.37 (dd, J=8.41, 5.77 Hz, 2H). m/z (ESI) 184 (M+H)+.

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