Application of 74115-12-1 , The common heterocyclic compound, 74115-12-1, name is 5-Chloro-3-hydroxypyridine, molecular formula is C5H4ClNO, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Example 12 Preparation of Compound 7 (0241) (0242) To a 0 C. solution of 5-chloro-3-hydroxypyridine (3.00 g, 23.16 mmol) in tetrahydrofuran (90 mL) was added lithium tert-butoxide (1.0 M in THF, 23.16 ml, 23.16 mmol) dropwise, so as to maintain the internal reaction temperature below 10 C. (0243) In a separate flask, compound 12a (10.0 g, 22.1 mmol) was dissolved in tetrahydrofuran (50.0 mL). This solution was added dropwise to the lithium phenoxide solution over 2 min below 10 C. The cooling bath was then removed. This solution was then added dropwise to the lithium phenoxide solution over a 5 minute period while maintaining the internal reaction temperature below 10 C. The mixture was aged at 0-10 C. for 2 hours, then 0.5M aqueous citric acid (150 mL) and MTBE (100 mL) were added. The organics were dried over MgSO4, filtered, concentrated in vacuo, and purified using silica gel chromatography (0:100 to 70:30 EtOAc:Hexanes) to provide compound 7 (8.1 g, 22.4 mmol, 92% yield). 1H-NMR delta (ppm)(DMSO-d6): 1.11 (6H, dd, J=6.3, 3.3 Hz), 1.20 (3H, d, J=7.1 Hz), 3.89-3.97 (1H, m), 4.79-4.84 (1H, m), 6.71 (1H, dd, J=14.2, 10.1 Hz), 7.24 (1H, t, J=7.4 Hz), 7.29 (2H, d, J=8.1 Hz), 7.42 (2H, t, 7.8 Hz), 7.86 (1H, d, J=2.0 Hz), 8.47 (1H, s), 8.53 (1H, d, J=2.1 Hz).
The synthetic route of 74115-12-1 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; EDWARDS, John Simon; MULLENS, Peter Richard; CLEATOR, Edward; MAGUIRE, Courtney K.; SCOTT, Jeremy Peter; ZHONG, Yong; FREY, Lisa F.; DORMER, Peter G.; KLAPARS, Artis; ASHLEY, Eric; QIAN, Pu; MERCK SHARP & DOHME CORP.; MERCK SHARP & DOHME LIMITED; Edwards, John; Mullens, Peter Richard; Cleator, Ed; Simmons, Bryon L.; Maguire, Courtney K.; Scott, Jeremy Peter; Yasuda, Nobuyoshi; Zhong, Yong-Li; Frey, Lisa F.; Dormer, Peter G.; Brunskill, Andrew; Klapars, Artis; Qian, Puneet; Zhang, Yi; Wan, Baoqiang; (23 pag.)US2017/275327; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem