Methyl 5-bromo-2-methoxy-4-pyridinecarboxylate

To a solution of methyl 5-bromo-2-hydroxy-pyridine-4-carboxylate (20.0 g, 86.2 mmol) in toluene (200 mL) was added silver carbonate (30.9 g, 112.1 mmol) and iodomethane (18.4 g, 129.3 mmol). The reaction mixture was stirred at 50 °C for 15 h and filtered. The filtrate was concentrated under reduced pressure. The residue was purified bycolumn chromatography (silica gel, 100-200 mesh, 0 to 30percent ethyl acetate in petroleum ether) to give methyl 5-bromo-2-methoxy-pyridine-4-carboxylate (16.4g, 77percent) as a white solid, used as is in the next step.To a solution of 5-bromo-2-methoxy-pyridine-4-carbaldehyde (23.5 g, 108.8 mmol) in MeOH (100 mL) were successively added a solution of ITo a solution of methyl 5-bromo-2-hydroxy-pyridine-4-carboxylate (20.0 g, 86.2 mmol) in toluene (200 mL) was added silver carbonate (30.9 g, 112.1 mmol) and iodomethane (18.4 g, 129.3 mmol). The reaction mixture was stirred at 50 °C for 15 h and filtered. The filtrate was concentrated under reduced pressure. The residue was purified bycolumn chromatography (silica gel, 100-200 mesh, 0 to 30percent ethyl acetate in petroleum ether) to give methyl 5-bromo-2-methoxy-pyridine-4-carboxylate (16.4g, 77percent) as a white solid, used as is in the next step.To a solution of 5-bromo-2-methoxy-pyridine-4-carbaldehyde (23.5 g, 108.8 mmol) in MeOH (100 mL) were successively added a solution of ITo a solution of methyl 5-bromo-2-hydroxy-pyridine-4-carboxylate (20.0 g, 86.2 mmol) in toluene (200 mL) was added silver carbonate (30.9 g, 112.1 mmol) and iodomethane (18.4 g, 129.3 mmol). The reaction mixture was stirred at 50 C for 15 h and filtered. The filtrate was concentrated under reduced pressure. The residue was purified bycolumn chromatography (silica gel, 100-200 mesh, 0 to 30% ethyl acetate in petroleum ether) to give methyl 5-bromo-2-methoxy-pyridine-4-carboxylate (16.4g, 77%) as a white solid, used as is in the next step.A mixture of lithium hydroxide monohydrate (13.98g, 333.25mmol) and methyl 5- bromo-2-methoxy-pyridine-4-carboxylate (16 .40g, 66 .65mmol) in tetrahydrofuran (30mL) /water (6mL) was stirred at 25 C for 2 h. The mixture was concentrated under reduced pressure. The aqueous residue was diluted with water (l0mL) and adjusted to pH=4 by addition of hydrochloric acid (2 M, 80 mL). The mixture was extracted with ethyl acetate (3 x 1 0mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford crude 5-bromo-2-methoxy-pyridine-4-carboxylic acid (9.62g, 62%) as brown oil. LCMS RT = 0.448 mi m/z = 231.9 [M + H]. LCMS (5 to 95% acetonitrile in water + 0.03% trifluoacetic acid over 1.5 mins) retention time 0.448 mi ESI+ found [M+H] = 231.9.To a solution of 5-bromo-2-methoxy-pyridine-4-carbaldehyde (23.5 g, 108.8 mmol) in MeOH (100 mL) were successively added a solution of I2 (35.9 mg, 141.4 mmol) in MeOH (75 mL) and a solution of KOH (15.9 g, 282.8 mmol) in MeOH (75 mL) at 0 C. The resulting mixture was stirred for 1 hr at 0 C and the reaction was quenched with saturated aqueous NaHS03. The resulting mixture was diluted with DCM (400 mL). The separated organic phase was washed with H20 (150 mL) and brine (150 mL), dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by flash column (eluting with PE:EA=20: 1, v:v) to give To a solution of

Molecular Weight:246.06
XLogP3:1.7
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:244.96876
Monoisotopic Mass:244.96876
Topological Polar Surface Area:48.4
Heavy Atom Count:13
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes