Propargyl alcohol → HCID 12181442, compound

25.8 g of 3-bromopyridine, 3.47 g of 10% palladium-activated carbon (Pd—C), 3.41 g of triphenyl phosphine, 56.4 g of potassium carbonate and 1.24 g of copper iodide were dissolved in 250 ml of 50% aqueous dimethoxyethane solution, followed by stirring at room temperature for 30 minutes. Then, 22.9 g of propargyl alcohol was added thereto, followed by heating at 80° C. for 16 hours under stirring. After cooling, the insolubles were removed, the dimethoxyethane was distilled off in vacuo. Thereafter, the resultant mixture was acidified by adding hydrochloric acid and, after washing with toluene, the mixture was alkanized again with the addition of potassium carbonate, followed by extracting with ethyl acetate. The extract thus obtained was purified by column chromatography to obtain 19.6 g (90%) of 1-(3-pyridyl)-1-propyn-3-ol. Then, 19.6 g of the 1-(3-pyridyl)-1-propyn-3-ol obtained above and 72 mg of 4-dimethylamino pyridine were dissolved in 150 ml of tetrahydrofuran and 14.8 g of diketene was added thereto at 0° C., followed by stirring at room temperature for 2 hours. After the solvent was distilled off in vacuo, the resultant product was extracted with ethyl acetate to obtain 3-(3-pyridyl)-2-propynyl ester. Then, this compound was dissolved, without purification, in 500 ml of tetrahydrofuran, followed by blowing gaseous ammonia thereto at 0° C. for 4 hours. After allowing to stand at room temperature for 3 days, the solvent was distilled off in vacuo and the residue was purified with Florisil (magnesium silicate manufactured by Florisine to obtain the target compound in an amount of 22.2 g (73%).

1. temperatureby heating at 80° C. for 16 hours
2. stirringunder stirring
3. temperatureAfter cooling
4. customthe insolubles were removed
5. distillationthe dimethoxyethane was distilled off in vacuo
6. additionby adding hydrochloric acid
7. washafter washing with toluene
8. additionthe mixture was alkanized again with the addition of potassium carbonate
9. extractionby extracting with ethyl acetate
10. extractionThe extract thus
11. customobtained
12. customwas purified by column chromatography

ORD record

ord-6e3b308a5d154062ac883c783ab55f91

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06306853B1