4-(Benzyloxy)-2-bromonicotinonitrile synthesis

Yield:727737-51-1 83%

Reaction Conditions:

Stage #1: benzyl alcoholwith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 0.0833333 h;
Stage #2: 2,4-dibromopyridine-3-carbonitrile in N,N-dimethyl-formamide;mineral oil at 0 - 20; for 1 h;

Steps:

2

To a suspension of NaH (1.756 g, 45.818 mmol, mineral oil 60%) in DMF (200 ml) cooled at 0 ⁰C, was added benzyl alcohol (4.542 g, 42 mmol). The resulting mixture was stirred for 5 min. Then, intermediate compound Dl (10 g, 38.18 mmol) was added. The resulting reaction mixture was gradually warmed to r.t. and stirred for 1 h, then quenched with NH₄Cl (aqueous sat. solution) and diluted with H₂O. The resulting mixture was extracted with Et₂O. The organic layer was separated, dried (Na₂SO₄) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution Of NH₃ in MeOH up to 1% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D2 (9.2 g, 83%).

References:

WO2010/130423,2010,A1 Location in patent:Page/Page column 49