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

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)+.

1. customThe ice bath was then removed
2. temperatureThe reaction mixture was cooled to 0° C.
3. additiondiluted with EtOAc
4. customquenched by the addition of saturated aqueous ammonium chloride solution
5. customThe solution was partitioned between EtOAc and saturated aqueous NaHCO3 solution
6. customThe aqueous phase was separated
7. extractionextracted with EtOAc
8. washThe combined organic phases were washed with brine
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford a yellow-brown oil
13. washwashing with MeOH
14. concentrationThe ammonia solution was concentrated

ORD-Eintrag

ord-ff837d9ce9a54632af712c25cb718dba

Quelldatensatz

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09340549B2