ChemicalBook CAS DataBase List 2-Chloro-5-fluoronicotinonitrile

2-Chloro-5-fluoronicotinonitrile synthesis

7synthesis methods

Product Name:2-Chloro-5-fluoronicotinonitrile
CAS Number:791644-48-9
Molecular formula:C6H2ClFN2
Molecular Weight:156.54

2-CHLORO-5-FLUORO-PYRIDINE-3-CARBALDEHYDE

851484-95-2
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$50.00/100 mg

791644-48-9
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$16.00/100mg

Yield:791644-48-9 89.5%

Reaction Conditions:

Stage #1:2-chloro-5-fluoropyridine-3-carbaldehyde with hydroxylamine hydrochloride in ethanol;water at 20; for 1 h;
Stage #2: with 1,1'-carbonyldiimidazole in dichloromethane for 1 h;Inert atmosphere;Reflux;

Steps:

1.14.A Step A: Preparation of 2-chloro-5-fluoronicotinonitrile.
To a solution of hydroxylamine hydrochloride (0.410 g, 5.902 mmol) in H₂0 (7.5 mL) was added a solution of 2-chloro-5-fluoronicotinaldehyde (0.856 g, 5.365 mmol) in EtOH (10 mL) in one portion. White solid came out. After stirring at room temperature for 1 h, water (10 mL) was added. The white solid was filtered off to give the intermediate (0.92 g).To a suspension of the solid obtained above in CH₂C1₂ (15 mL) under nitrogen was added carbonyl diimidazole (1.044 g, 6.438 mmol) and the suspension became a clear solution. The mixture was heated at reflux for 1 h and concentrated. The residue was purified by silica gel chromatography (15% hexanes/EtOAc) to give the title compound (0.752 g, 4.804 mmol, 89.5% yield) as white solid. 'H NMR (CDC1₃ , 400 MHz) ? ppm 7.75 (dd, / = 6.8 and 3.0 Hz, IH), 8.49 (d, 7 = 3.0 Hz, IH).

References:

ARENA PHARMACEUTICALS, INC.;JONES, Robert M.;BUZARD, Daniel J.;HAN, Sangdon;KIM, Sun Hee;LEHMANN, Juerg;ZHU, Xiuwen WO2013/55910, 2013, A1 Location in patent:Page/Page column 106; 107

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