3-Bromo-5-ethoxypyridine

Under a nitrogen atmosphere, sodium (4.60 g, 200 mmol) was added to absolute ethanol (100 mL) at 0-5 °C, and the stirring mixture was allowed to warm to ambient temperature over 18 h. To the resulting solution was added 3, 5-dibromopyridine (31.5 g, 133 mmol), followed by DMF (100 mL). The mixture was heated at 70°C for 48 h. The brown mixture was cooled, poured into water (600 mL), and extracted with ether (3 x 500 mL). The combined ether extracts were dried (Na2S04), filtered, and concentrated by rotary evaporation. Purification by vacuum distillation afforded 22.85 g (85.0percent) of an oil, bp 89-90°C at 2.8 mm Hg (lit. bp 111°C at 5 mm Hg, see K. Clarke, et al., J. Chem. Soc. 1885 (I960))Preparation of 3-ethoxy-2-methoxy-5-bromopyridine (Compound 1004) [0091] As shown in step 2-i of Scheme 2, to 4.0 g (0.1 mol, 60percent in mineral oil) NaH in a 100 mL DMF suspension was added 10 mL of an absolute ethyl alcohol (4.6 g, 0.1 mol)/DMF solution at RT. After the evolution of hydrogen gas, the reaction mixture was stirred at RT for 30 minutes and the resulting ethoxide solution transferred to a solution of 3, 5- dibromopyridine (11.84g, 0.05 mol, obtained from Aldrich Chemical Co.) in 100 mL DMF at 60 As shown in step 2-i of Scheme 2, to 4.0 g (0.1 mol, 60percent in mineral oil) NaH in a 100 mL DMF suspension was added 10 mL of an absolute ethyl alcohol (4.6 g, 0.1 mol)/DMF solution at RT. After the evolution of hydrogen gas, the reaction mixture was stirred at RT for 30 minutes and the resulting ethoxide solution transferred to a solution of 3, 5- dibromopyridine (11.84g, 0.05 mol, obtained from Aldrich Chemical Co.) in 100 mL DMF at 60 As shown in step 2-i of Scheme 2, to NaH (4.0 g, 60percent in mineral oil, 0.1 mol) in a 100 mL DMF suspension was added 10 mL of an absolute ethyl alcohol (4.6 g, 0.1 mol)/DMF solution at RT. After the evolution of hydrogen gas, the reaction mixture was stirred at RT for 30 minutes and the resulting ethoxide solution transferred to a solution of 3, 5- dibromopyridine (11.84 g, 0.05 mol, obtained from Aldrich Chemical Co.) in 100 mL DMF at 60°C. The reaction was stirred at 60°C for 4 hours and then allowed to come to RT. Brine and ethyl acetate were added and the organics were partitioned, dried over MgS0Under a nitrogen atmosphere, sodium (4.60 g, 200 mmol) was added to absolute ethanol (100 mL) at 0-5° C, and the stirring mixture was allowed to warm to ambient temperature over 18 h. To the resulting solution was added 3, 5-dibromopyridine (31.5 g, 133 mmol), followed by DMF (100 mL). The mixture was heated at 70° C for 48 h. The brown mixture was cooled, poured into water (600 mL), and extracted with ether (3 x 500 mL). The combined ether extracts were dried (Na2SO4), ] filtered, and concentrated by rotary evaporation. Purification by vacuum distillation afforded 22.85 g (85.0 percent) of an oil, bp 89-90° C at 2.8 mm Hg (lit. bp 111° C at 5 mm Hg, see K. Clarke, et al., J. Chem. Soc. 1885 (1960)). 5-Ethoxy-3-bromopyridine A solution of 5-bromopyridin-3-ol (70 g, 402 mmol), KA solution of 5-bromopyridin-3-ol (70 g, 402 mmol), KA solution of 5-bromopyridin-3-ol (70 g 402 mmol) KA mixture of EXAMPLE 8A A mixture of 5-bromopyridin-3-ol (500 mg, 2.87 mmol), ethyl bromide (375 mg, 3.44 mmol) and K2CO3 (793 mg, 5.74 mmol) in DMF (15 mL) was stirred at 60 C for 18 hours. To the mixture was added (i-Pr)20 (20 mL). The mixture was washed with 2N NaOH (aqueous, 5 mL x 2), the aqueous phase was re-extracted with (i-Pr)20 (10 mL x 2). The combined organic layers were washed with H20 (10 mL x 3), brine (10 mL), dried over Na2S04, filtered and concentrated to give

Molecular Weight:202.05
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:200.97893
Monoisotopic Mass:200.97893
Topological Polar Surface Area:22.1
Heavy Atom Count:10
Complexity:99.6
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes