Chlorotrimethylsilane → HCID 24828509, Verbindung

Temperatur

-78 °C

An ether solution (40 mL) of 1-bromo-3-fluoro-5-(trifluoromethyl)benzene (2.0 g, 8.23 mmol) was stirred in an oven-dried round bottom flask at −78° C. under Ar. n-BuLi (2.5 M in hexanes, 3.6 ml, 9.05 mmol, 1.1 eq) was added dropwise. The resulting solution was stirred at −78° C. for 30 min. A solution of 4-fluoro-3-(trifluoromethyl)benzonitrile (1.55 g, 8.23 mmol, 1.0 eq) in Et2O (5 mL) was added dropwise. The resulting reddish mixture was stirred at −78° C. for 2 h. TMSCl (pretreated with Et3N (TMSCl:Et3N=10:1, v:v), 1.14 mL, 1.2 eq) was added dropwise. The dry ice bath was removed, and the resulting slurry was stirred at room temperature for 2 h. The reaction was cooled to −78° C. and a solution of benzyl magnesium chloride in THF (2.0 M, 8.4 m, 2 eq) was added dropwise. The resulting mixture was slowly warmed up to room temperature and stirred at room temperature overnight. (NHC5 (100 mL) was added. The mixture was stirred at room temperature for 30 min, extracted with Et2O (2×), washed with 1N NaOH, H2O and brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, hexanes:ethyl acetate) to give 1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (1.6 g, yield: 44%). LC-MS ESI 3.42 min 429.2 (M-NH3+H); 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 7.66 (dd, J=6.7, 2.3 Hz, 1H), 7.49-7.59 (m, 1H), 7.45 (s, 1H), 7.18-7.30 (m, 6H), 6.74 (d, J=6.9 Hz, 2H), 3.57 (m, 2H).

1. stirringThe resulting reddish mixture was stirred at −78° C. for 2 h
2. customThe dry ice bath was removed
3. stirringthe resulting slurry was stirred at room temperature for 2 h
4. temperatureThe reaction was cooled to −78° C.
5. temperatureThe resulting mixture was slowly warmed up to room temperature
6. stirringstirred at room temperature overnight
7. addition(NHC5 (100 mL) was added
8. stirringThe mixture was stirred at room temperature for 30 min
9. extractionextracted with Et2O (2×)
10. washwashed with 1N NaOH, H2O and brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated to dryness
14. customThe residue was purified by flash column chromatography (silica gel, hexanes:ethyl acetate)

ORD-Eintrag

ord-9c37636816964d9681e20a99256d854b

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08642576B2