4-(2'-Fluoro-5'-chlorobenzoyl)-5-hydroxynicotinic acid → 4-(2'-Fluoro-5'-chlorobenzyl)-5-hydroxynicotinic acid

To a stirred suspension of zinc dust (>230 mesh; 100 mg) in 75% formic acid (1.3 mL), at 80° C. (external bath temperature), 4-(5'-chloro-2'-fluorobenzoyl)-5-hydroxynicotinic acid of Preparative Example 26 (100 mg) is added portionwise during 5 minutes. Three further portions of zinc dust (3×50 mg) are subsequently added every 30 min. Stirring is continued for further 10 minutes after the last addition of zinc dust and the reaction mixture is then partitioned between ethyl acetate (10 mL) and 0.5N HCl (10 mL). The aqueous phase is extracted three times with ethyl acetate (3×10 mL), saturated with NaCl and further extracted with ethyl acetate (10 mL). The combined organic phases are washed with brine (10 mL), dried over Na2SO4 and concentrated to dryness. The residue is triturated in acetone (2 mL) and allowed to crystallize overnight. The white solid is collected by filtration, washed with methyl tert-butyl ether and dried under vacuum at 100° C. 4-(2'-fluoro-5'-chlorobenzyl)-5-hydroxynicotinic acid is obtained as a white solid (47 mg).

1. customat 80° C.
2. customis added portionwise during 5 minutes
3. customthe reaction mixture is then partitioned between ethyl acetate (10 mL) and 0.5N HCl (10 mL)
4. extractionThe aqueous phase is extracted three times with ethyl acetate (3×10 mL)
5. extractionsaturated with NaCl and further extracted with ethyl acetate (10 mL)
6. washThe combined organic phases are washed with brine (10 mL)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated to dryness
9. customThe residue is triturated in acetone (2 mL)
10. customto crystallize overnight
11. filtrationThe white solid is collected by filtration
12. washwashed with methyl tert-butyl ether
13. customdried under vacuum at 100° C

ORD-Eintrag

ord-c575c86ebaca48d2b1bccbd8b6ec797d

Quelldatensatz

uspto-grants-1997_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05596097