反应详情

To a solution of 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid (9.1 g, 45.7 mmol) in DMF (40 mL) was added cesium carbonate (22.3 g, 68.5 mmol) followed by benzyl bromide (11.7 g, 8.1 mL, 68.5 mmol) and reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed sequentially with H2O (3×10 mL), brine solution. The organics were separated and dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 10-20% EtOAc-hexanes to provide benzyl 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoate (2.8 g, 21%) ESI-MS m/z calc. 288.2. Found 289.3 (M+1)+; Retention time: 1.79 min (3 min run). To a solution of benzyl 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoate (2.8 g, 9.71 mmol) in MeOH (50 mL) was added palladium on carbon (100 mg, 0.09 mmol) and the reaction mixture was subjected to an atmosphere of hydrogen for 16 hours. The catalyst was removed via filtration over Celite® and the solvent removed in vacuo to provide 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid (1.8 g, 96%) as a white solid. ESI-MS m/z calc. 198.2. Found 199.9 (M+1)+; Retention time: 0.91 minutes (3 min run).

1. customThe reaction mixture was partitioned between EtOAc and H2O
2. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
3. washThe combined organic layers were washed sequentially with H2O (3×10 mL), brine solution
4. customThe organics were separated
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe resulting residue was purified by silica gel column chromatography
9. washeluting with 10-20% EtOAc-hexanes