Hydrochloric Acid → (αR)-4-Chloro-2-fluoro-α-methylbenzenemethanamine

To a solution of (S)-N-((R)-1-(4-chloro-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (5.4 g, 19.4 mmol) in methanol (150 mL) at 0° C. was added a solution of hydrochloric acid in p-dioxane (4.0 M in p-dioxane, 19.4 mL, 77.6 mmol). The reaction was slowly warmed to room temperature and stirred at room temperature for 18 h. The solvent removed in vacuo, and the crude material was dissolved in saturated aqueous sodium bicarbonate and dichloromethane. The mixture was stirred for 45 min to give a clear solution. The phases were separated, and the aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was used without further purification (3.1 g, 92%, >96% ee, determined by Mosher's method).

1. customThe solvent removed in vacuo
2. dissolutionthe crude material was dissolved in saturated aqueous sodium bicarbonate
3. stirringThe mixture was stirred for 45 min
4. customto give a clear solution
5. customThe phases were separated
6. extractionthe aqueous layer was extracted with dichloromethane (2×100 mL)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was used without further purification (3.1 g, 92%, >96% ee, determined by Mosher's method)

ORD record

ord-c78e012334a8412e9100cef7bd2b08d6

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08685959B2