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

75302-64-6

791644-48-9

Example 3A: Synthesis of 2-chloro-5-fluoronicotinonitrile 81.2 mL (582.25 mmol) of triethylamine was added to a 783 mL dichloromethane suspension containing 46.2 g (264.66 mmol) of 2-chloro-5-fluoronicotinonitrile, and the mixture was subsequently cooled to 0°C. Under continuous stirring, 41.12 mL (291.13 mmol) of trifluoroacetic anhydride was slowly added dropwise, and after completion of the dropwise addition, the reaction mixture was kept at 0 °C with continued stirring for 1.5 hours. After completion of the reaction, the reaction mixture was washed twice with saturated aqueous sodium bicarbonate (391 mL each time), and the organic phase was dried and concentrated under reduced pressure to give the crude product. The final product was 2-chloro-5-fluoronicotinonitrile with a yield of 42.1 g and 90% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ= 8.66 (dd, 1H), 8.82 (d, 1H).

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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75302-64-6
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$240.00/100mg

791644-48-9
158 suppliers
$16.00/100mg

References

38186-88-8 Synthesis