Acetic Anhydride → 1,2-Benzisoxazole, 6-bromo-3-(trifluoromethyl)-

To a flask containing 1-(4-bromo-2-hydroxy-phenyl)-2,2,2-trifluoro-ethanone oxime (2.64 g, 9.29 mmol) was added acetic anhydride (14 mL) and the reaction mixture stirred for 18 h at rt. The reaction mixture was concentrated and taken up in toluene and again concentrated to yield the acylated intermediate. This intermediate was dissolved in pyridine (15 mL) and triethylamine (3.2 mL) and heated at 112° C. for 4.5 h. The reaction mixture was concentrated and the residue was taken up in toluene and again concentrated the residue was then partitioned between EtOAc (25 mL) and HCl (1 N aq., 25 mL). The layers were separated and the organic layer washed with HCl (1 N aq., 25 mL). The combined water layers were then extracted with EtOAc (25 mL×2) and the combined organic layers were washed with brine (15 mL), dried (Na2SO4) and concentrated. The crude material was purified (FCC) to yield the title compound (44 mg, 17%).

1. concentrationThe reaction mixture was concentrated
2. concentrationagain concentrated
3. customto yield the acylated intermediate
4. concentrationThe reaction mixture was concentrated
5. concentrationagain concentrated the residue
6. customwas then partitioned between EtOAc (25 mL) and HCl (1 N aq., 25 mL)
7. customThe layers were separated
8. washthe organic layer washed with HCl (1 N aq., 25 mL)
9. extractionThe combined water layers were then extracted with EtOAc (25 mL×2)
10. washthe combined organic layers were washed with brine (15 mL)
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated
13. customThe crude material was purified (FCC)

ORD-Eintrag

ord-1553bf4240484a4b9231c5bace7f28ad

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08598202B2