5-Fluoropyridine-2-carboxaldehyde

5-Fluoro-pyridine-2-carboxylic acid (200 mg, 1.13 mmol) was mixed with ethanol (6 mL) and 4 M [HC1] in dioxane (0.5 mL) at 90 [°C] for 20 h. The mixture was concentrated and mixed with saturated sodium carbonate and dichloromethane. The dichloromethane layer was washed with brine, dried to give 94 mg (49.3percent) of 5-fluoro-pyridine-2-carboxylic acid ethyl ester. To 5-fluoro-pyridine-2-carboxylic acid ethyl ester (94 mg, 0.556 mmol) in dichloromethane (4.0 [ML), ] [1] M DIBAL in toluene (1.23 mL, 1. 23 mmol) was added at room temperature and the mixture was stirred for 30 min. The reaction mixture was quenched with 2 M sodium carbonate and extracted with dichloromethane. The dichloromethane was dried and concentrated to give 39 mg (54.7percent) of crude 5-fluoro- pyridine-2-carbaldehyde which could be used for the next step reaction without further purification. GC-MS [(M+)] : 1255-Fluoro-pyridine-2-carbaldehyde p. 3600-35; DIBAL (1 M toluene solution, 8. 2 mL, 8.2 mmol) was added dropwise to a cold (-78 °C) solution of 5-fluoro-pyridine-2-carbonitrile (l. Og, 8.2 mmol) in CH2Cl2 (50 mL) and the resulting misture was stirred at-78 °C for 3 h, with an additional 0.25 equivalents of DIBAL added after 0.5 and 1 h. The reaction was quenched with 1 N HCl (20 mL) and stirred for 2.5 h. The aqueous phase was basified with solid NaHCO3 and the product was extracted with CH2Cl2. (An emulsion formed that required filtration before extraction could be performed). The combined organics were washed with brine and dried (Na2SO4) and filtered. Purification was performed by flash column chromatography over silica gel, eluting with 2 percent EtOAc/hexanes to yield the product (200 mg, 20 percent, colourless solid which melts just above room temperature and was volatile under high vacuum resulting in a lower yield than expected). 1H NMR (CDC13, 300 MHz): 8 = 7. 59 (ddd, J = 8, 2, 1 Hz, 1H), 8.04 (ddd, J = 8, 5, 0.5 Hz, 1H), 8. 64 (d, J = 2 Hz, 1H), 10.00 (apparent dd, J = 1, 1 Hz, 1H).

Molecular Weight:125.10
XLogP3:0.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:125.027691913
Monoisotopic Mass:125.027691913
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes