Ammonium Acetate → 1-[2-(2,4-Difluorophenyl)phenyl]ethan-1-amine

Temperatur

60 °C

To a stirred solution of 1-(2′,4′-difluoro-1,1′-biphenyl-2-yl)ethanone (3.67 g, 15.8 mmol) in anhydrous methanol (200 mL) was added solid ammonium acetate (12.2 g, 158 mmol). The reaction mixture was heated at 60° C. for one hour, followed by the addition of a methanolic solution of sodium cyanoborohydride (5 mL, 1.99 g, 31.6 mmol). After 16 hours, the methanol was removed in vacuo and aqueous ammonium hydroxide was added. The aqueous phase was extracted with diethyl ether (3×200 mL) until the amine was no longer present in the aqueous phase. The combined organic phase was washed with 2 N aqueous hydrochloric acid (3×100 mL) and the aqueous phases combined. The solid formed during the acid wash was determined to be the dialkyated amine and was segregated from the aqueous phase. Aqueous sodium hydroxide was added to the acidic aqueous phase until the solution was neutralized to pH 8 to 9. The basic aqueous phase was extracted with diethyl ether until the primary amine was no longer detected in the aqueous phase. The combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to afford a clear oil that was used without further purification;

1. customthe methanol was removed in vacuo and aqueous ammonium hydroxide
2. additionwas added
3. extractionThe aqueous phase was extracted with diethyl ether (3×200 mL) until the amine
4. washThe combined organic phase was washed with 2 N aqueous hydrochloric acid (3×100 mL)
5. customThe solid formed during the acid
6. washwash
7. additionAqueous sodium hydroxide was added to the acidic aqueous phase until the solution
8. extractionThe basic aqueous phase was extracted with diethyl ether until the primary amine
9. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford a clear oil that
13. customwas used without further purification

ORD-Eintrag

ord-6b8b6c7bcf9d49c9883530f34b069708

Quelldatensatz

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06894061B2