反应详情

A solution of 12.2 g (0.05 mole) 2-[3-(phenylmethoxy)phenoxy]ethanol and 5.6 g (0.555 mole) of triethylamine in 100 ml of THF was cooled to 0° C. with stirring and treated dropwise with 6.4 g (0.055 mole) of mesyl chloride over a 20-min period. The mixture was stirred at 10° C. or less for 1 hr, then filtered. The filtrate was combined with a slurry of 0.10 mole of imidazole sodium salt in 50 ml of THF and the mixture was heated at reflux for 8 hr. The 50 ml of THF and the mixture was heated at reflux for 8 hr. The cooled reaction mixture was filtered and the filtrate was partitioned between ethyl acetate/ether and water. The organic layer was concentrated to give 14.7 g (100%) of crude intermediate. This syrup (13.0 g) was dissolved in 100 ml of methanol and hydrogenated at 40° C. and 45 psi H2 using 1 g of 10% Pd/C catalyst. This mixture was filtered, and the filtrate was concentrated to give 9.0 g (100%) of crude, crystalline product. A portion was recrystallized from toluene/methyl isobutyl ketone to give the title compound as white crystals, mp 125.0° C.-127.0° C.

1. stirringThe mixture was stirred at 10° C. or less for 1 hr
2. filtrationfiltered
3. temperaturethe mixture was heated
4. temperatureat reflux for 8 hr
5. temperatureat reflux for 8 hr
6. customThe cooled reaction mixture
7. filtrationwas filtered
8. customthe filtrate was partitioned between ethyl acetate/ether and water
9. concentrationThe organic layer was concentrated
10. customto give 14.7 g (100%) of crude intermediate
11. filtrationThis mixture was filtered
12. concentrationthe filtrate was concentrated
13. customto give 9.0 g (100%) of crude, crystalline product
14. customA portion was recrystallized from toluene/methyl isobutyl ketone