Reaction #168202

Reaction equation

2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile

4-methoxyphenylboronic acid

potassium phosphate tribasic monohydrate

→

2-chloro-6-(4-methoxyphenyl)-4-(4-phenoxyphenyl)nicotinonitrile

Yield 68.0%

Solvents

N,N-dimethylformamide

ethyl acetate

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Washwashed with water (15 mL), brine (15 mL)
3. 3
   Dryingdried (MgSO4)
4. 4
   Concentrationconcentrated
5. 5
   Washeluting with 5-30% ethyl acetate in hexanes

Procedure

A mixture of 2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile (110 mg, 0.322 mmol), 4-methoxyphenylboronic acid (53.9 mg, 0.355 mmol), palladium tetrakis(triphenylphosphine) (16.30 mg, 0.016 mmol) and potassium phosphate tribasic monohydrate (0.484 mL, 0.967 mmol) in N,N-dimethylformamide (3 mL) was heated under nitrogen to 100° C. for 15 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (80 mL), washed with water (15 mL), brine (15 mL), dried (MgSO4), and concentrated. Silica gel chromatography, loading with toluene and eluting with 5-30% ethyl acetate in hexanes, gave 2-chloro-6-(4-methoxyphenyl)-4-(4-phenoxyphenyl)nicotinonitrile as white solid (90 mg, 68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.94-8.22 (2H, m), 7.69 (1H, s), 7.56-7.65 (2H, m), 7.42 (2H, t, J=7.97 Hz), 7.18-7.26 (1H, m), 7.06-7.19 (4H, m), 7.02 (2H, δ, J=8.80 Hz), 3.90 (3H, s); MS (ES+) m/z: 413 (M+H); LC retention time: 4.423 min (analytical HPLC Method A).

Source