Methyl 6-bromonicotinate

Methyl 6-bromonicotinate. In a 100 ml round-bottomed flask were placed 6-bromonicotinic acid (540 mg, 2.7 mmol), DCM (20 ml), and DMF (1 drop). Oxalyl chloride (1 ml) was added, resulting in vigorous gas evolution. The reaction was stirred for 1 hr after which the solvent was removed in vacuo. The residue was treated with MeOH and the solvent removed in vacuo. The residue was partitioned between DCM and saturated NaHCψ3 and the organic layer was dried over NaTo a solution of 6-bromonicotinic acid (14.3, 2.0 g, 9.90 mmol) in methanol (20 mL), sulfuric acid (2.0 mL) was added at 0 °C and the reaction mixture was heated at 70 °C for 3 h. After completion, the reaction mixture was cooled to room temperature and solvent was removed under reduced pressure. The crude was diluted with water (50 mL) and pH was adjusted to 6 by saturated solution of sodium bicarbonate .The reaction mixture was extracted with ethyl acetate (100 mL), organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude. The crude was purified by washings with diethyl ether and pentane to afford methyl 6- bromonicotinate (14.2) as yellow solid. Yield: 1.10 g, 52.0percent.Step 2a. Dissolve 6-chloropyridine-3-carboxylic acid methyl ester (6.86 g, 40 mmol) in toluene (100 mL) and heat to 90°C. Add phosphorous oxybromide (25 g, 87 mmol) in several portions and continue heating for 3 hours. Cool the reaction to room temperature and pour onto ice water. Extract the reaction with ethyl acetate and wash organics again with water then NAHC03. COMBINE organics, dry over MGS04, filter, and evaporate to orange solid (8.1 g, 94percent) which is an 8: 1 mixture OF 6-BROMOPYRIDINE-3-CARBOXYLIC acid methyl ester : 6-CHLOROMOPYRIDINE-3-CARBOXYLIC acid methyl ester BY LH NMR. Combine the mixture as obtained above (0.225 g, 1.04 mmol) with hexamethylditin (0.375 g, 1.15 mmol), Pd (OAC) 2 (21 mg, 0.09 mmol), and triphenylphosphine (25 mg, 0.09 mmol) in toluene (5 mL). Purge with N2 and stir at 80°C for 18 hours. Cool reaction to room temperature. Add a solution of 1-BROM-2, 6- difluorobenzene (250 mg, 1.29 mmol) in toluene (1 mL) followed by Pd (OAC) 2 (21 mg, 0.09 mmol) and triphenylphosphine (25 mg, 0.09 mmol). Purge with N2 and stir at 80°C for an additional 18 hours. Cool reaction to room temperature. Evaporate the solvent and purify by column chromatography (silica, 10percent ethyl acetate in hexane) to give 50 mg (20percent yield) OF 6- (2, 6-difluorophenyl) pyridine-3-carboxylic acid ethyl ester. Hydrolyze the ester with IN sodium hydroxide solution (0.22 mL, 0.22 mmol) in methanol (3 mL) at room temperature for 3 days. Remove the volatiles under vacuum and combine the RESIDUE with IN hydrochloric acid solution. Collect the white solid by filtration, wash with water, and dry under vacuum to give 30 mg (63percent yield) of the title compound. MS (ES): m/z 235.9 (M+H).6-bromonicotinic acid (1.00g, 4.95mmol) was dissolved in N, N-dimethylformamide (30 mL) was added methyl iodide (0.703g, 4.95mmol) and potassium carbonate (1.03g, 7.43mmol). The reaction was stirred at 20 deg.] C for 12 hours. The reaction solution was added water (100 mL) was diluted, extracted with ethyl acetate (30mLx3), The organic phase was dried over anhydrous sodium sulfate, filtered, The filtrate was concentrated under reduced pressure, purified by silica gel column chromatography separation gel (2: 1 petroleum ether / ethyl acetate, Rf = 0.5) to give 6-bromo-nicotinic acid methyl ester (1.00 g of, white solid), yield: 94percent.Methyl iodide (1.06 g, 0.007 mole) was added at 0 - 5 °C to a stirred suspension of 6-bromonicotinic acid (1.0 g, 0.004 mol) and K

Molecular Weight:216.03
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:214.95819
Monoisotopic Mass:214.95819
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes