ChemicalBook CAS DataBase List 2-Hydroxynicotinic acid

2-Hydroxynicotinic acid synthesis

11synthesis methods

Product Name:2-Hydroxynicotinic acid
CAS Number:609-71-2
Molecular formula:C6H5NO3
Molecular Weight:139.11

13466-43-8 Synthesis

13466-43-8
250 suppliers
$6.00/1g

124-38-9
129 suppliers
$175.00/23402

609-71-2
380 suppliers
$5.00/5g

Yield:609-71-2 79%

Reaction Conditions:

Stage #1:3-bromo-pyridin-2-ol with isopropylmagnesium chloride in tetrahydrofuran at 0; for 0.166667 h;
Stage #2: with n-butyllithium in tetrahydrofuran;hexane at -20; for 0.5 h;
Stage #3:carbon dioxide in tetrahydrofuran;hexane at -20; for 0.5 h;

Steps:

2-Hydroxy-nicotinic acid (3n)
To a solution of 3-bromo-2-hydroxypyridine (0.76 g, 4.4 mmol, 1.0 equiv.)in dry THF (20 mL) at 0 C was added a 2 M solution of i-PrMgCl in THF (2.2 mL, 4.4 mmol, 1.0 equiv.)during 5 min. The clear solution was stirred at that temperature for an additional 5 min, and a2.5 M solution of n-BuLi in hexanes (3.5 mL, 8.8 mmol, 2.0 equiv.) was added dropwise during 5 min,while maintaining the temperature below 20 C. The resulting mixture was stirred at that temperaturefor 0.5 h, dry CO2 (0.20 g, 1.0 equiv.) was added to 20 C. The resulting mixture was warmed to20 C in 0.5 h and quenched with water (6 mL). After stirring the mixture below 20 C for 10 min,the phases were separated and the water phase was extracted one additional time with ethyl acetate.The resulting suspension was allowed to reach room temperature and fitered through a 0.5 1 cmpad of silica gel eluted with 10 mL of ethyl acetate. The ltrate was concentrated and the residue waspurified by flash chromatography on silica gel (eluent: petroleum ether/ethyl acetate = 10:1) to affordproduct 3n as off-white solid, 0.48 g (yield: 79%), m.p.: 255-257 C. 1H-NMR (600 MHz, DMSO) 14.76 (s, 1H), 13.38 (s, 1H), 8.38 (dd, J = 7.2, 2.0 Hz, 1H), 7.95 (dd, J = 6.3, 2.0 Hz, 1H), 6.68 (t, J = 6.7 Hz,1H). 13C-NMR (151 MHz, DMSO) 165.46, 165.04, 146.61, 141.95, 117.12, 109.09.

References:

Tian, Qingqiang;Shang, Suqin;Wang, Huajun;Shi, Guoqiang;Li, Zhiyao;Yuan, Jianyong [Molecules,2017,vol. 22,# 11,art. no. 1952] Location in patent:supporting information

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2942-59-8 Synthesis