反应详情

温度

55 °C

1-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperidin-4-ol (200 mg) and pyridin-4-ol (65 mg) were mixed with THF (3 ml), and triphenylphosphine (250 mg) was added thereto. A 1.9M DIAD/toluene solution (0.5 ml) was added dropwise to the reaction mixture, followed by stirring at 55° C. overnight. Then, a 1M TBAF/THF solution (1 ml) was added to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and diethyl ether and 1M hydrochloric acid were added thereto. The organic layer was separated by a liquid separation operation, and the aqueous layer was washed with diethyl ether twice again. The aqueous layer was adjusted to a pH of around 10 by the addition of a 4 M aqueous NaOH solution, and extracted with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain {2-fluoro-3-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}methanol (84 mg).

1. additionwas added
2. stirringby stirring at room temperature for 1 hour
3. concentrationThe reaction mixture was concentrated under reduced pressure, and diethyl ether and 1M hydrochloric acid
4. additionwere added
5. customThe organic layer was separated by a liquid separation operation
6. washthe aqueous layer was washed with diethyl ether twice again
7. additionThe aqueous layer was adjusted to a pH of around 10 by the addition of a 4 M aqueous NaOH solution
8. extractionextracted with CHCl3
9. dry with materialThe organic layer was dried over Na2SO4
10. concentrationconcentrated under reduced pressure
11. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)