反应详情

step 5a—Trifluoroacetic anhydride (1.3 mL, 12 eq.) and H2O2 (0.24 mL, 2.5 eq.) were combined at 0° C. and stirred for 2 h. The mixture containing trifluoroperacetic acid was added to a mixture of 5-(3-bromo-2-fluoro-6-formyl-phenoxy)-N,N′-di-tert-butyl-isophthalamide from step 4 (0.4 g, 0.81 mmol) and potassium phosphate (2.2 g, 20 eq.) in DCM at 0° C. and the reaction mixture stirred for 5 h. The reaction mixture was diluted with DCM and washed sequentially with sodium bisulfite and brine. The solution containing the formate ester was concentrated in vacuo and the residue was dissolved in THF (4 mL) and a solution of LiOH.H2O (0.43 g, 3 eq.) in H2O (1 mL) was added to the reaction mixture and stirred for 5 h. The reaction mixture was diluted with EtOAc and washed with HCl (aqueous), water, and brine. The organic phase was dried (Na2SO4), filtered and evaporated to afford 0.300 g (75%) of 5-(3-bromo-2-fluoro-6-hydroxy-phenoxy)-N,N′-di-tert-butyl-isophthalamide (D-2b, Ar=3,5-di-tert-butyl-dicarboxamido-phenyl).

1. customwere combined at 0° C.
2. stirringthe reaction mixture stirred for 5 h
3. washwashed sequentially with sodium bisulfite and brine
4. additionThe solution containing the formate ester
5. concentrationwas concentrated in vacuo
6. dissolutionthe residue was dissolved in THF (4 mL)
7. stirringstirred for 5 h
8. washwashed with HCl (aqueous), water, and brine
9. dry with materialThe organic phase was dried (Na2SO4)
10. filtrationfiltered
11. customevaporated