2-METHYLISONICOTINALDEHYDE

Reference Example 151 To a solution OfNaIOExample 117 To a stirred solution of 4-bromo-2-methylpyridine (1.00 g, 5.81 mmol) in anhydrous diethyl ether (70 mL) was added n-BuLi (2.5 M, 2.56 mL, 6.39 mmol) at -78 °C under N2. After stirring at -78 °C for 15 mi DMF (0.54 mL, 6.92 mmol) was added slowly. The mixture was stirred for another 30 mm and warmed to 0 °C. The mixture was quenched with 20 mL of aq. NaHCO3, extracted with EA (50 mL x 2). The combined organics was washed with brine (50 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated. The resulted residue was purified by column chromatography eluted with PE/EA (5:1) to give the title product (210 mg, 30percent) as a light yellow solid. ‘HNMR (400 MHz, CDCl) 10.05 (s, 1H), 8.76 (d, J=4.8 Hz, 1H), 7.56 (s, 1H), 7.51 (d, J=4.8 Hz, 1H), 2.68 (s, 3H)Intermediate H: Preparation of 2-methylisonicotinaldehyde Under a nitrogen atmosphere, to a solution of 4-bromo-2-methylpyridine (2.00 g, 11.63 mmol) in anhydrous EtA solution of chromium (Vl) oxide (2 g, 20 mmol), pyridine (4 mL, 50 mmol) and 20 mL of dichloromefhane was stirred at room temperature for 30 minutes. To this mixture, cooled with an ice water bath, (2-methyl-pyridin-4-yl)-methanol (48, 0.5 g, 4.0 mmol) in 5 mL of dichloromethane was added. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was cooled with an ice water bath and diluted with ethyl acetate, then filtered through a pad of Celite, The filtrate was concentrated under vacuum and the residue was purified by silica gel chromatography eluting with hexanes and ethyl acetate to provide the desired compound as a colorless liquid (21b, 0.1 g, 20percent), General procedure: In a test tube, substrate (1.0 mmol) and CuCl2•2H2O(0.10 mmol) were dissolved in DMSO (3.0 mL). O2 balloon (1 atm) was attached at top of the test tube, and inner atmosphere was replaced by O2. After stirring at 100 °C for 45 hours, reaction mixture was diluted by CH2Cl2 (20 mL) and washed with sat. Na2CO3 aq (10 mL).The separated water phase was then extracted with CH2Cl2 (10 mL×2). The combined organicphase was washed with brine (20 mL) and dried over Na2SO4. After removal of Na2SO4 byfiltration, evaporation of the solvent gave brown oil, from which the desired product wasisolated by silica column chromatography (eluent: EtOAc / n-Hexane = 1 / 10 to 1 / 1).

Molecular Weight:121.14
XLogP3:0.6
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