2-FORMYL-5-PICOLINE

For the synthesis of 5-methylpyridin-2-carbaldehyde (B; n = 1 ; R1 , R2, R4 = H; R3 = Me) 50 g (290 mmol) 2-bromo-5-methylpyridinβ (B2; R1, R2, R4 = H; R3 = Me) was dissolved in 2500 ml diethylether and cooled to -78°C. Then, 150 ml (380 mmoi) nBuLi was added drop wise and the reaction mixture was stirred for 2hrs at -78° C. DMF (31.5 ml, 407 mmol) was added drop wise and after the reaction mixture was allowed to warm to room temperature, water was added to the reaction mixture. Both, organic and aqueous layer were separated and the water layer was extracted with ethyl acetate for three times. All organic layers were combined, washed with brine, dried over NaIntermediate 161 : 5-methyl-2-pyridinecarbaldehvde; 5 g of 5-bromo-2-methylpyridine (29.1 mmole, Aldrich), dissolved in 60 mL of dry THF.The solution was cooled to -78To the 0.25 M 5-methyl-2-pyridinylmagnesium bromide of THF solution (20 mL, 5 [MMOL), ] DMF (0.773 mL, 10 mmol) was added at room temperature under argon. The reaction mixture was stirred for 10 min. and concentrated in vacuo. The residue was quenched with saturated ammonium chloride and dichloromethane. The organic layer was dried and the product was purified by silica gel column chromatography with 20 percent ethyl acetate in hexanes to give 379 mg (62.6percent) of the title compound. GC-MS [(M+)] : 121.To a solution of 41 (5-methylpyridin-2-yl)methanol [Example 2, Step 2] (2 g, 16.24 mmol, 1.00 equiv) in 42 chloroform (25 mL) was added 43 MnOTo a solution of 41 (5-methylpyridin-2-yl)methanol [Example 2, Step 2] (2 g, 16.24 mmol, 1.00 equiv) in 42 chloroform (25 mL) was added 43 MnO2 (18.39 g, 211.53 mmol, 13.00 equiv). The mixture was stirred overnight at 50 C. The solids were filtered out. The filtrate was concentrated under vacuum to afford 500 mg (25%) of 44 1.23 g of 5-methylpyridine-2-methanol, 2 mol% of vanadium nitrate (relative to 5-methylpyridine-2-methanol), was added to a 50 mL reaction tube. Add 5 mL of diethylamine, fill the air ball, close the reaction tube, and warm to 50 C with stirring, and keep it for 6 h.After the reaction was completed, it was cooled to room temperature. Sampling was analyzed using gas chromatography. Conversion rate of 5-methylpyridine-2-methanol 95.2%, The latter was dissolved in 150 ml of dichloromethane and, after mixing with 8 g of active MnO2, was refluxed for 7.5 hours. The solution was filtered hot and the filtrate rotated in. 7 g of 5-methyl-pyridine-2-aldehyde were obtained.General procedure: A solution of 2 mmol of the corresponding substituted pyridine-2-carbaldehyde in 30 mL of anhy-drous ethanol was added to 0.36 g (1 mmol) of com-pound 4 and few drops (3-4) of glacial acetic acid. The mixture was heated under reflux and stirring for 3 h. After cooling, the solid precipitate was filtered off, washed with water, dried, and purified by recrystal-lization from ethanol.

Molecular Weight:121.14
XLogP3:1.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:121.052763847
Monoisotopic Mass:121.052763847
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:103
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes