1-(6-Chloropyridin-3-yl)cyclobutanecarbonitrile synthesis

Yield:485828-75-9 52%

Reaction Conditions:

Stage #1: (6-chloro-pyridin-3-yl)-acetonitrilewith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 0.666667 h;
Stage #2: 1,3-dibromo-propane in N,N-dimethyl-formamide;mineral oil at 20; for 2 h;

Steps:

52.1 Step 1. Synthesis of 83-1

To a solution of 2-chloro-5-pyridineacetonitrile (14.3 g, 94 mmol) in dimethylformamide (120 mL) at 0 °C, was added sodium hydride (8.6 g, 216 mmol, 60% in oil) portion-wise over 20 minutes. The mixture was stirred for a further 20 minutes and 1,3-dibromopropane (20 g, 98.7 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 2 h. The reaction was quenched by water (50 mL). Ethyl acetate (200 mL) was added and the organic phase was washed with water (100 mL) and brine (100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on a silica gel column (petroleum ether to petroleum ether/ ethyl acetate = 3/1) to afford the desired product (9.4 g, 52% yield).

References:

WO2017/139414,2017,A1 Location in patent:Paragraph 00360-00361