2-Chloro-3-fluoropyridin-4-ol Chemical Properties

Boiling point:

351.2±37.0 °C(Predicted)

Density 

1.517±0.06 g/cm3 (20 ºC 760 Torr)

storage temp. 

Inert atmosphere,Room Temperature

pka

6.32±0.10(Predicted)

form 

solid

color 

White

Safety Information

HS Code 

2933399990

2-Chloro-3-fluoropyridin-4-ol Usage And Synthesis

Synthesis

General procedure for the synthesis of 2-chloro-3-fluoro-4-hydroxypyridine: 2-chloro-3-fluoropyridine (2 mmol) was dissolved in anhydrous THF (10 mL) under anhydrous conditions and the solution was cooled to -78 °C. A hexane solution of lithium diisopropylammonium (LDA; 2.2 mmol) was slowly added to this solution at the same temperature. After the reaction mixture was stirred at -78 °C for 2 h, trimethoxyborane (0.48 mL) was added and stirring was continued for 2 h. The reaction mixture was then cooled to -78 °C. Subsequently, peracetic acid (0.72 mL; 32% in dilute acetic acid) was added and the mixture was slowly warmed to 0 °C with stirring and kept for 1 hour. Upon completion of the reaction, the mixture was cooled to 20 °C and aqueous sodium conidiosulfite solution (0.8 g dissolved in 2 mL of water) was added dropwise. The reaction mixture was extracted with ethyl acetate and the organic phases were combined, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography with an eluent ratio of 1:19 methanol:dichloromethane to afford the target product 2-chloro-3-fluoro-4-hydroxypyridine as a white solid in 80% yield. The structure of the product was determined by 1H NMR (d6-DMSO): δ 11.86 (br s, 1H, OH), 7.89 (d, J = 5.3 Hz, 1H, C6-H), 6.95 (t, J = 5.8 Hz, 1H, C5-H); 19F NMR (d6-DMSO): δ 141.29 (s); ESI-MS: 148(M + 1)+ Confirmation.

References

[1] Patent: WO2009/103950, 2009, A1. Location in patent: Page/Page column 22-23
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 5, p. 2185 - 2195
[3] Dalton Transactions, 2012, vol. 41, # 21, p. 6549 - 6557
[4] Journal of Fluorine Chemistry, 2015, vol. 173, p. 29 - 34
[5] Tetrahedron Letters, 2010, vol. 51, # 40, p. 5230 - 5233

2-Chloro-3-fluoropyridin-4-ol(1184172-46-0)Related Product Information

• 2-CHLORO-3-FLUOROPYRIDINE-5-BORONIC ACID
• 2-CHLORO-4-IODO-3-METHYLPYRIDINE
• 2-CHLORO-3-FLUORO-4-IODOPYRIDINE
• 2-Chloro-4,6-dimethylpyridine
• 2-Chloro-3-fluoropyridine-4-carboxylic acid
• 2-CHLORO-3-FLUORO-4-FORMYLPYRIDINE
• 2-Chloro-3-fluoro-5-hydroxypyridine
• 2-Chloro-4-methylpyridine-5-boronic acid