反应详情

A suspension of methyl 4-bromo-3-methylbenzoate (4 g; 17.5 mmol; 1 eq.), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)isoxazole (Fluorochem 11035; 4.28 g; 19.2 mmol; 1.1 eq.), potassium carbonate (12.1 g; 87.3 mmol; 5 eq.) and Pd(PPh3)4 (2.02 g; 1.75 mmol; 0.1 eq.) in toluene (20 mL) and water (20 mL) was refluxed for 4 hours. The reaction mixture was cooled down to room temperature and filtered through a pad of CELITE which was further washed with toluene (200 mL). The filtrate was concentrated in vacuo and the residue taken up in Ethyl acetate (250 mL). The organic layer was washed with sat. aq. NaHCO3 (100 mL), water (100 mL) and brine (100 mL) then dried over magnesium sulfate and concentrated in vacuo. The residue (3 g; 12.2 mmol; 1 eq.) was taken up in EtOH (90 mL), sodium hydroxide (5M; 7.34 mL; 36.7 mmol; 3 eq.) was added and the reaction mixture was stirred at 60° C. for one hour. After concentration in vacuo, the residue was taken up in water (200 mL) and the aqueous phase was washed with Ethyl acetate then acidified to pH 2 with conc. HCl. The solution was concentrated to ca. 100 mL and the precipitate filtered off and dried. Trituration in Et2O and filtration afforded the title compound as a beige solid.

1. temperaturewas refluxed for 4 hours
2. filtrationfiltered through a pad of CELITE which
3. washwas further washed with toluene (200 mL)
4. concentrationThe filtrate was concentrated in vacuo
5. washThe organic layer was washed with sat. aq. NaHCO3 (100 mL), water (100 mL) and brine (100 mL)
6. dry with materialthen dried over magnesium sulfate
7. concentrationconcentrated in vacuo
8. concentrationAfter concentration in vacuo
9. washthe aqueous phase was washed with Ethyl acetate
10. concentrationThe solution was concentrated to ca. 100 mL
11. filtrationthe precipitate filtered off
12. customdried
13. filtrationTrituration in Et2O and filtration