反应详情

Heat a mixture of 3-[2-(2-bromo-5-fluoro-phenoxymethyl)-phenyl]-acrylic acid ethyl ester (0.25 mol, 94 g), sodium acetate (0.37 mol, 30 g, 1.5 equiv.), tetra-n-butylammonium bromide (0.25 mol, 81 g), and palladium (II) acetate (7 mmol, 1.7 g, 3 mol %) in N-methylpyrrolidinone (850 mL) at 100-110° C. for 6 h. Cool to room temperature, dilute with water (1 L), filter through diatomaceous earth, and wash with ethyl acetate (2 L). Transfer the filtrate to a separatory funnel, add water (500 mL) and separate the layers. Wash the organic layer with water (2×1.5 L), dry over anhydrous sodium sulfate, filter through a silica pad, wash with ethyl acetate (1.5 L) and concentrate to dryness. To the residual solid add hexanes (1 L), refrigerate for 2 h, filter, rinse with hexanes (500 mL), and dry at 50° C./20 mm Hg to obtain the title compound (64.3 g, 87%). LC-MS m/z 299.0 [M+H]+.

1. temperatureHeat
2. filtrationfilter through diatomaceous earth
3. washwash with ethyl acetate (2 L)
4. additionTransfer the filtrate to a separatory funnel, add water (500 mL)
5. customseparate the layers
6. washWash the organic layer with water (2×1.5 L)
7. dry with materialdry over anhydrous sodium sulfate
8. filtrationfilter through a silica pad
9. washwash with ethyl acetate (1.5 L)
10. concentrationconcentrate to dryness
11. additionTo the residual solid add hexanes (1 L)
12. filtrationfilter
13. washrinse with hexanes (500 mL)
14. customdry at 50° C./20 mm Hg