Reaktion #325986

Reaktionsgleichung

(R)—N-(2-(4-cyanophenyl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide

LAH

→

(R)—N-(2-(4-(aminomethyl)phenyl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide

Ausbeute 36.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigequenched by addition of 2 N LiOH
2. 2
   SonstigeThe solid was removed by filtration
3. 3
   Einengenthe filtrate was concentrated
4. 4
   SonstigeThe resulting residue was purified by prep HPLC (YMC Sunfire 5μ C18 30×100 mm column, eluting with 20-90% MeOH/H2O containing 0.1% TFA, 10 min gradient, flow rate 40 mL/min, wavelength 220 nm)

Vorschrift

To a solution of (R)—N-(2-(4-cyanophenyl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide, prepared as described in Procedure 56, (77% yield, 20 mg, 0.02 mmol) in THF (1.5 mL) at rt was added LAH (1.0 M in THF). The reaction mixture was stirred at rt for 5 h, then quenched by addition of 2 N LiOH. The solid was removed by filtration and the filtrate was concentrated. The resulting residue was purified by prep HPLC (YMC Sunfire 5μ C18 30×100 mm column, eluting with 20-90% MeOH/H2O containing 0.1% TFA, 10 min gradient, flow rate 40 mL/min, wavelength 220 nm) to provide (R)—N-(2-(4-(aminomethyl)phenyl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide (Example 300) as a colorless film (5 mg, 36% yield). LCMS: RT=1.8 min [M+H] 713.26 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.1% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.31 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm). 1H NMR (400 MHz, CD3OD) δ ppm 7.95 (1H, d, J=6.59 Hz), 7.46-7.48 (1H, m), 7.36 7.41 (2H, m), 7.22 (1H, t, J=9.45 Hz), 7.16 (2H, d, J=7.91 Hz), 6.99 (2H, dd, J=16.48, 9.45 Hz), 6.93 (1H, s), 6.73 (2H, d, J=7.91 Hz), 6.21H, t, J=49.7 Hz), 4.01-4.06 (1H, m), 3.93-3.99 (3H, m).

Quelle