3-Hydroxypyridine → 3-(1-Methyl-3-pyrrolidinyloxy)-pyridine

Temperature

-20 °C

To 629 mg (2.4 mmol) of PPh3 in 13 mL of dry THF at −20° C. was added 378 μL (2.4 mmol) of DEAD dropwise. The solution was allowed to stir 10 min. at −20° C. After 10 min, a solution containing 220 μL (2.0 mmol) of 1-methyl-3-hydroxypyrrolidine and 2 mL of dry THF was added dropwise. The solution was again allowed to stir 10 min at −20° C. After 10 min, to the solution was added 190 mg (2.0 mmol) of 3-hydroxypyridine at once. The solution was allowed to stir at room temperature overnight. Next day, solvent was removed under reduced pressure. The crude product was purified by flash chromatography (9:1, CHCl3:MeOH) to obtain 260 mg (72.9%) of a clear oil: 1H NMR (300 MHz, CDCl3) δ 8.26 (1H, d, J=2.6 Hz), 8.20 (1H, d, J=4.2 Hz), 7.22-7.13 (2H, m), 4.85 (1H, m), 2.89-2.76 (3H, m), 2.48-1.95 (3H, m), 2.40 (3H, s); Mass spectrum (ESI) m/z 179.6 (M+H+).

1. waitAfter 10 min
2. additionwas added dropwise
3. stirringto stir 10 min at −20° C
4. waitAfter 10 min
5. stirringto stir at room temperature overnight
6. customNext day, solvent was removed under reduced pressure
7. customThe crude product was purified by flash chromatography (9:1, CHCl3:MeOH)

ORD record

ord-91ac6303422440df819757124b9fe427

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06888001B2