3-FLUORO-2-FORMYLPYRIDINE Chemical Properties

Melting point:

49 °C

Boiling point:

112°C/50mmHg(lit.)

Density 

1.269±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

soluble in Methanol

form 

Solid

pka

1.25±0.10(Predicted)

color 

White to Green to Brown

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C6H4FNO/c7-5-2-1-3-8-6(5)4-9/h1-4H

InChIKey

OZIMPUNGBUYCSP-UHFFFAOYSA-N

SMILES

C1(C=O)=NC=CC=C1F

CAS DataBase Reference

31224-43-8(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

Hazard Note 

Harmful

HS Code 

2933399990

3-FLUORO-2-FORMYLPYRIDINE Usage And Synthesis

Uses

3-Fluoropyridine-2-carboxaldehyde is used to prepare taxoids derived from 9β-dihydrobaccatin-9,10-acetals with anti-tumor activities. It is also an intermediate used to synthesize S-3578 derivatives with potent activities against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

Synthesis Reference(s)

Tetrahedron, 39, p. 2009, 1983 DOI: 10.1016/S0040-4020(01)91919-2

Synthesis

To a solution of DABCO (8.8 g, 78.2 mmol) in anhydrous ether (250 mL) was slowly added n-BuLi (1.6 M hexane solution, 49 mL, 78.2 mmol) at -25 °C. The reaction mixture was stirred between -25 and -10°C for 45 minutes and subsequently cooled to -70°C. At -70 °C, 3-fluoropyridine (5.9 mL, 71 mmol) was added dropwise to the above reaction solution. The reaction temperature was maintained between -70 and -60 °C and stirring was continued for 1.5 hours. After that, DMF (11.0 mL, 2.0 eq.) was added to the reaction system. After stirring at -70 °C for 1.0 h, the reaction was quenched by slow addition of water (150 mL) and gradually warmed to room temperature. Upon completion of the reaction, the organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane (5 x 100 mL). All organic layers were combined, washed with saturated saline and dried with anhydrous sodium sulfate. After the solvent was removed by concentration under reduced pressure, the crude product was purified by silica gel column chromatography using ethyl acetate/hexane gradient elution to afford 3-fluoropyridine-2-aldehyde (5.4 g, 55-60% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.54-7.57 (m, 2H), 8.61 (d, J = 2.20 Hz, 1H), 10.20 (s, 1H).

References

[1] Patent: US2010/227894, 2010, A1. Location in patent: Page/Page column 55
[2] Patent: WO2006/114706, 2006, A1. Location in patent: Page/Page column 47-48
[3] Tetrahedron, 1983, vol. 39, # 12, p. 2009 - 2021
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 23, p. 6998 - 7003
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 6, p. 1852 - 1856

3-FLUORO-2-FORMYLPYRIDINE(31224-43-8)Related Product Information

• 3-FLUORO-PYRIDINE-2-CARBOXYLIC ACID METHYL ESTER
• 2-Acetyl-3-fluoropyridine
• 3-Fluoro-6-bromo-2-pyridinecarboxaldehyde
• 6-Chloro-3-fluoro-pyridine-2-carboxylic acid
• 3,5-Difluoropicolinic acid
• 3-FLUOROPYRIDINE-2-CARBOXYLIC ACID
• 3-FLUORO-2-FORMYLPYRIDINE
• 5-BROMO-3-FLUOROPICOLINIC ACID
• 5-FLUORO-2-FORMYLPYRIDINE
• 5-Chloro-2-fluoropyridine-3-carboxaldehyde
• 3-FLUORO-5-FORMYLPYRIDINE
• 4-IODO-2-FLUORO-3-FORMYLPYRIDINE
• 2-FLUORO-5-FORMYLPYRIDINE
• 4-FLUORO-3-FORMYLPYRIDINE
• 2-CHLORO-5-FLUORO-4-FORMYLPYRIDINE
• 2-FLUORO-6-FORMYLPYRIDINE
• 2-FLUORO-4-FORMYLPYRIDINE
• 2-CHLORO-5-FLUORO-3-FORMYLPYRIDINE