反应详情

温度

0 °C

To a solution of methyl 5-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate (for a synthesis see Preparation 12(b)) (698 mg, 2.457 mmol) in DCM (20 ml) stirred under N2 at 0° C. was added DIBAL-H (1.5 M solution in toluene, 4.91 ml, 7.37 mmol) dropwise. The reaction mixture was stirred at 0° C. for 3 h and at room temperature overnight. The reaction mixture was diluted with MeOH and concentrated under reduced pressure. The residue was treated with a 1N HCl solution and extracted twice with EtOAc. The combined organic phases were dried over anhydrous Na2SO4 and concentrated under reduced. The crude material was purified by Flashmaster chromatography on a 10 g silica gel cartridge using hexane/EtOAc 95:5 as eluent to afford [5-bromo-6-(trifluoromethyl)-3-pyridinyl]methanol (297 mg, 54%) no pure enough to be used in the next step. The title compound was re-purified by preparative HPLC (column XTerra 30×150 mm, gradient elution: 30 to 80% CH3CN/H2O, uv detection 254 nm) to give the title compound (157 mg, 24%).

1. stirringThe reaction mixture was stirred at 0° C. for 3 h and at room temperature overnight
2. concentrationconcentrated under reduced pressure
3. additionThe residue was treated with a 1N HCl solution
4. extractionextracted twice with EtOAc
5. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
6. concentrationconcentrated
7. customThe crude material was purified by Flashmaster chromatography on a 10 g silica gel cartridge