反应详情

A mixture of 2-methoxy-5-pyridin-2-yl-pyridine (550 g) and a 4 mol/L aquesous solution of hydrochloric acid (2.4 L) was heated under reflux for 3 hours. After cooling the reaction solution, and washed with tert-butylmethyl ether (2.2 L). To the aqueous layer was added 8 mol/L aqueous solution of sodium hydroxide (1.1 L) under cooling with ice-water, and then the mixture was washed twice with tert-butylmethyl ether (2.2 L). Then, it was adjusted to pH 8 with concentrated hydrochloric acid (310 ml) and 8 mol/L aqueous solution of sodium hydroxide (100 ml), followed by partitioning between 1-butanol (4.5 L) and brine (1.8 L). The aqueous layer was extracted again with 1-butanol (4.5 L), and the combined organic layer was evaporated at 45-50° C. To the resulting residue was added tert-butylmethyl ether (2.2 L), to give crystals. The resulting crystals were collected by filtration under reduced pressure and air-dried at 60° C. Then, water (1.6 L) was added thereto to dissolve under heating. Then the mixture was water-cooled, and recrystallized. The resulting crystals were collected by filtration under reduced pressure and air-dried at 60° C., to give 188 g (66%) of the title compound as grayish white crystals.

1. temperatureunder reflux for 3 hours
2. temperatureAfter cooling the reaction solution
3. washwashed with tert-butylmethyl ether (2.2 L)
4. additionTo the aqueous layer was added 8 mol/L aqueous solution of sodium hydroxide (1.1 L)
5. temperatureunder cooling with ice-water
6. washthe mixture was washed twice with tert-butylmethyl ether (2.2 L)
7. customby partitioning between 1-butanol (4.5 L) and brine (1.8 L)
8. extractionThe aqueous layer was extracted again with 1-butanol (4.5 L)
9. customthe combined organic layer was evaporated at 45-50° C
10. additionTo the resulting residue was added tert-butylmethyl ether (2.2 L)
11. customto give crystals
12. filtrationThe resulting crystals were collected by filtration under reduced pressure
13. customair-dried at 60° C
14. additionThen, water (1.6 L) was added
15. dissolutionto dissolve
16. temperatureunder heating
17. temperaturecooled
18. customrecrystallized
19. filtrationThe resulting crystals were collected by filtration under reduced pressure
20. customair-dried at 60° C.