3-(5-Cyanopyridin-3-yl)benzyl alcohol synthesis

Yield:-

Reaction Conditions:

Stage #1: p-hydroxymethylphenylboronic acidwith potassium carbonate in 1,2-dimethoxyethane;water; for 0.333333 h;
Stage #2: tetrakis(triphenylphosphine) palladium⁽⁰⁾ in 1,2-dimethoxyethane;water at 80; for 16 h;

Steps:

2a.1

To (4-hydroxymethylphenyl)boronic acid (Combi-B locks; 10.0g, 65.8mmol) in DME/H₂O (60mL, 2: 1 ) was added 5-bromo-2-methoxypyridine (Combi-Blocks; 13.6g, 72.4mmol) and potassium carbonate (45.5g, 328.9mmol). The reaction was degassed with N₂ for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.760g, 0.66mmol) was added and the reaction was further degassed for 15 minutes. The reaction was then heated to 80°C for 16 hours under N₂. LCMS confirmed the formation of the product. The reaction was partitioned between H₂O and EtOAc and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO₄, filtered, concentrated, and triturated with EtOAc to give the desired product.

References:

WO2008/67566,2008,A1 Location in patent:Page/Page column 92