Methyl 5-bromonicotinate

white powder

Preparation 2; SYNTHESIS OF 5-[4-(5-FLUORO-2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]-NICOTINIC ACID METHYL ESTER; A. A mixture of 5-bromonicotinic acid (1.000 g, 4.95 mmol) and 5 drops of concentrated sulfuric acid in anhydrous methanol (30 mL) was refluxed for 3 hours. The reaction mixture was concentrated in vacuo, diluted with 20 mL of water and extracted with ethyl acetate. The organic phase was dried and concentrated. The residue obtained was used for next step reaction without further purification. Yield 0.965 g, 90percent.To the solution of 24a (500mg, 2.48mmol) in methanol (2OmL) was added thionyl chloride (590mg, 4.95mmol) at 0-5Example-1 5-Bromo-nicotinic acid methyl ester (Example 1); 5-Bromo-nicotinic acid (300mg, 1. 5mmol) was added methanol (6ml) and concentrated H2SO4 (1. lml). This reaction mixture was then heated at reflux for overnight. After cooling down, about 5ml of concentrated NaHCO3 solution was added to adjust the PH to 7-8. The product was then extracted with DCM (20ml). Removal of the solvent gave the product as white solid in 81 percent yield. IR: 3450, 3047, 1722, 1577, 1419, 1311, 1107, 1016, 955, 764, 688; IH NMR (270 MHz, CDC13): 9.12 (s, 1H, H-2), 8. 85 (m, 1H, H-6), 8.44 (m, 1H, H-4), 3.99 (s, 3H, Cl3) ; 13C NMR (100.4 MHz, CDC13) : 164.4 (CO), 154.4 (C2), 148.7 (C6), 139. 6 (C4), 127.4 (C3), 120.7 (C5), 52.9 (CH3) ; MS: m/z (FAB+) 216.2 (M+).The solution of 5-bromonicotinic acid (3.0g, 15mmol) was dissolved in anhydrous methanol (20ml), 98percent concentrated sulfuric acid (4ml) was added dropwise at room temperature, and the mixture was stirred for 10min, then heated to reflux for 15h, Adding water to dilute, adding saturated sodium bicarbonate aqueous solution, adjusting pH to neutral, extracting with ethyl acetate, washing with water, drying with anhydrous sodium sulfate, filtering, distilling off the solvent and subjecting the residue to silica gel column chromatography to obtain white flaky crystals (2.6g, 80percent).To cooled methanol (20 mL, 0°C) was added dropwise concentrated H2S04 (2 mL). To the resulting clear solution was added 5-bromonicotinic acid (2 g, 10 mmol) and the mixture was refluxed for 3 h. After being cooled to room temperature, the solvent was evaporated and theresidue was partitioned between EtOAc and water. The organic layer was washed with saturatedNaHCO3 (a.q.), dried over Na2SO4 and concentrated to give methyl 5-bromonicotinate (1.5 g, yield:71percent). ‘H-NMR (CDC13, 400 MHz) 9.10 (d, J= 1.6 Hz, 1H), 8.81 (d, J= 2.4 Hz, 1H), 8.41 (t, J=2.4 Hz, 1H), 3.94 (s, 3H). MS (M+H): 216 / 218.To cooled methanol (20 mL, 0°C) was added dropwise concentrated H2S04 (2 mL). To the resulting clear solution was added 5-bromonicotinic acid (2 g, 10 mmol) and the mixture was refluxed for 3 h. After being cooled to room temperature, the solvent was evaporated and the residue was partitioned between EtOAc and water. The organic layer waswashed with saturated NaHCO3 (a.q.), dried over Na2SO4 and concentrated to give methyl 5- bromonicotinate (1.5 g, yield: 71percent). ‘H-NMR (CDC13, 400 MHz) 9.10 (d, J= 1.6 Hz, 1H), 8.81 (d, J= 2.4 Hz, 1H), 8.41 (t, J= 2.4 Hz, 1H), 3.94 (s, 3H). MS (M+H): 216 / 218.A solution of 5-bromonicotinic acid (10 g, 49.5 mmol) in MeOH (200mL) was cooled to 0 °C and conc. H5-Bromonicotinic acid (15.0 g, 74.3 mmol) was dissolved in DMF (200 mL), and the mixture was stirred at room temperature for 3 hours after adding potassium carbonate (15.4 g, 0.111 mol) and methyl iodide (9.25 mL, 0.149 mol). The mixture was diluted with ethyl acetate, and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give methyl 5-bromonicotinate (10.0 g, 63percent). ESI-MS: m/z 215, 217 [M + H]

Molecular Weight:216.03
XLogP3:1.4
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