2-(4-bromophenoxy)-5-(trifluoromethyl)pyridine

General procedure: (a) The starting compound 5-(4-bromophenoxy)-2-(trifluoromethyl)benzonitrile (30b) was prepared as shown below: Accordingly, a mixture of compound 40 (1.0 eq, Aldrich), compound 41 (2 g, 0.9 eq, Matrix Scientific) and K2CO3 (2 eq) in 25 mL of CH3CN was heated at 80° C. under argon for 14 hours. After cooling to room temperature, water (30 mL) was added, extracted with EtOAc (2*100 mL), concentrated and purified by column (silica gel, Hexanes, then Hexanes/EtOAc 10/1) to give compound 30b as a white solid (2.8 g, 81percent). 1H-NMR (400 MHz, CDCl3) delta: 7.75 (d, 1H, 8.8 Hz), 7.57-7.61 (m, 2H), 7.36-7.37 (m, 1H), 6.97-7.01 (m, 2H), 7.08-7.11 (m, 2H).(a) (E)-Ethyl 3-(l-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)- lH-indol-3-yl)acrylate (3) was prepared as follows: A mixture of compound 1 (Alfe Aesar, 0.5 g, 1.0 eq), compound 2, Cul (0.2 eq), K2C03 (3 eq), and dimethylglycine (Aldrich, 0.1 eq) in DMF (10 mL) was heated at 160 °C for 30 minutes under microwave. The mixture was dissolved in water/EtOAc (20 mL/100 mL). The organic layer was washed with brine, concentrated and purified by column (silica gel, EtOAc/hexane 1/10) to afford compound 3 as a white solid (0.4 g, 40percent): ?-NMR (400MHz, CDC13) ?: 8.42 (s, IH), 7.85 - 7.92 (m, 3H), 7.54 (s, IH), 7.47 - 7.51 (m, 3H), 7.23 - 7.29 (m, 4H), 7.06 (d, IH, 8.8Hz), 6.45 (d, IH, 16Hz), 4.23 (q, 2H, 7.1Hz), 1.29 (t, 3H, 7.2Hz).(b) 2-(4-Bromophenoxy)-5-(trifluoromethyl)pyridine (2) wasprepared by heating a mixture of 4-bromophenol (1.0 eq, Aldrich), 2-chloro-5- (trifluoromethyl)pyridine (0.9 eq, Aldrich), and K2C03 (2 eq) in 25 mL of CH3CN at 80 °C under argon for 14 hours. After cooling to room temperature, water (30 mL) was added, extracted with EtOAc (2x100 mL), concentrated and purified by column (silica gel, Hexanes, then Hexanes/EtOAc 10/1) to give compound 2: ?-NMR (400 MHz, CDCI3) ' 8.45 (s, IH), 7.94 (ddd, IH, 0.6, 2.6 & 8.6Hz), 7.56 (d, 2H, 8.9Hz), 7.05 - 7.08 (m, 3H)

Molecular Weight:318.09
XLogP3:3.6
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:316.96631
Monoisotopic Mass:316.96631
Topological Polar Surface Area:22.1
Heavy Atom Count:18
Complexity:267
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes