反应详情

Prepared as described for 4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one (Example 1) from 3,4-bis(benzyloxy)-6-{2-[2-fluoro-4-(trifluoromethyl)phenyl]-ethynyl}pyridazine (Intermediate 70) except that THF was used as the solvent. The reaction was filtered through diatomaceous earth flushing with further tetrahydrofuran and concentrated in vacuo. The residue was purified by column chromatography (silica C18 cartridge; eluting with 0-65% acetonitrile in water with acid modifier). The appropriate fractions were combined and concentrated in vacuo to remove the acetonitrile before the aqueous portion was extracted with ethyl acetate (×2), dried (MgSO4) and concentrated in vacuo. The resulting solid was recrystallised from a mixture of methyl tert-butyl ether and heptane to afford 6-{2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-4-hydroxy-2,3-dihydropyridazin-3-one as a cream solid (29% yield).

1. customPrepared
2. filtrationThe reaction was filtered through diatomaceous earth
3. customflushing with further tetrahydrofuran
4. concentrationconcentrated in vacuo
5. customThe residue was purified by column chromatography (silica C18 cartridge; eluting with 0-65% acetonitrile in water with acid modifier)
6. concentrationconcentrated in vacuo
7. customto remove the acetonitrile before the aqueous portion
8. extractionwas extracted with ethyl acetate (×2)
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo
11. customThe resulting solid was recrystallised from a mixture of methyl tert-butyl ether and heptane