反应详情

To a solution of 1-[3,5-difluoro-4-(methylthio)-phenyl]ethanone (prepared in Step 1 of Example 1) (6.2 g, 30 mmol) in 30% HBr in acetic acid (10 mL) was added bromine (4.8 g, 30 mmol) dropwise, and the reaction mixture stirred at room temperature for 45 minutes. The mixture was treated with water and extracted with ethyl acetate (1×250 mL, 1×100 mL). The combined extracts were washed with dilute sodium chloride solution, dried with magnesium sulfate, and concentrated. To the residue was added hexanes (100 mL) and the mixture concentrated. The residue was dissolved in 30% HBr in acetic acid (10 mL) and treated with bromine (0.80 g, 5.0 mmol). After stirring at room temperature for 30 minutes, the mixture was treated with water and extracted with dichloromethane (1×200 mL, 1×100 mL). The combined extracts were washed with water, dried with magnesium sulfate and concentrated. To the residue was added hexanes (100 mL), and the mixture concentrated. Purification of the product by silica gel chromatography using 10% ethyl acetate in hexanes gave 2-bromo-1-[3,5-difluoro-4-(methylthio)-phenyl]ethanone as an orange solid (7.2 g, 86%), MP 30.5-33.2° C. 1H NMR (CDCl3/400 MHz) 7.46-7.50 (m, 2H), 4.33 (s, 2H), 2.57 (t, 3H, J=1.1). ESHRMS m/z 278.9260 (M−H+, Calcd 278.9291). Anal. Calcd for C9H7BrF2OS: C, 38.45; H, 2.52. Found: C, 38.19; H, 2.34.

1. extractionextracted with ethyl acetate (1×250 mL, 1×100 mL)
2. washThe combined extracts were washed with dilute sodium chloride solution
3. dry with materialdried with magnesium sulfate
4. concentrationconcentrated
5. additionTo the residue was added hexanes (100 mL)
6. concentrationthe mixture concentrated
7. dissolutionThe residue was dissolved in 30% HBr in acetic acid (10 mL)
8. stirringAfter stirring at room temperature for 30 minutes
9. extractionextracted with dichloromethane (1×200 mL, 1×100 mL)
10. washThe combined extracts were washed with water
11. dry with materialdried with magnesium sulfate
12. concentrationconcentrated
13. additionTo the residue was added hexanes (100 mL)
14. concentrationthe mixture concentrated
15. customPurification of the product by silica gel chromatography