2,6-Dichloro-4-methoxypyridine

To a solution of 2, 4, 6-trichloropyridine (3.64 g, 20.0 mmol) in DMF (20 mL) at 0°C were slowly added NaH (60percent in mineral oil, 840 mg, 21 mmol) and MeOH (673 mg, 21 mmol). The mixture was stirred at room temperature for 16 h. The mixture was concentrated and partitioned between EtOAc (30 mL) and water (15 mL). The organic extracts were dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with ethyl acetate in hexane (0-5 percent) to afford the title compound (3.0 g, yield: 94percent).(37). A solution of sodium methoxide in MeOH (33 mL, 1M, 33 mmol) was added to a suspension of 2, 4, 6-trichloropyridine(36) (6.0 g, 33 mmol) in MeOH (82 mL) and stirred for 5 h at roomtemperature. The reaction mixture was poured into water(200 mL). The solid was removed by filtration, and the filtratewas concentrated under vacuum to give 37 (4.8 g, 80percent) as a whitesolid. 1H NMR (300 MHz, DMSO-d6) d 7.19 (s, 2H), 3.89 (s, 3H).LCMS 178.0, 180.1 [M+1]+.EXAMPLE 12-1Preparation of Compound 12-L [0672j A solution of 2, 4, 6-trichioropyridine (6.5 g, 36 mmol) in anhydrous methanol (20 mL) was added MeONa (2.9 g, 54 mmol) at 0°C. The reacton mixture was stirred at rt for 12 h. The reaction was quenched with dry ice, and the mixture was filtered. The solution was concentrated under reduced pressure, and the residue was dissolved in EA. The mixture was washed with water, and the organic layers were dried over NaSO4. The solvent was concentrated to give 12-L (4.2 g, 67percent).0221] A solution of 2, 4, 6-trichloropyridine (6.5 g, 36 mmol) in anhydrous methanol (20 mL) was added MeONa (2.9 g, 54 mmol) at 0°C. The reacton mixture was stirred at r.t. for 12 h. The reaction was quenched with dry ice, and the mixture was filtered. The solution was concentrated under reduced pressure, and the residue was dissolved in EA. The mixture was washed with water, and the organic layers were dried over NaS0Step 1: [243] Step C: 2, 6-Dichloro-4-methoxypyridine: A solution of phosphorus oxychloride (151 g) in 250 ml of dichloromethane was added to a mixture of 2-chloro-4-methoxypyridine 1 -oxide (13Og) and triethylamine (151 ml) in dichloromethane (1000 ml) at O

Molecular Weight:178.01
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:176.9748192
Monoisotopic Mass:176.9748192
Topological Polar Surface Area:22.1
Heavy Atom Count:10
Complexity:102
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes