反应详情

温度

120 °C

To a solution of methyl 4-bromo-2-hydroxy-5-(4-morpholinylmethyl)benzoate (may be prepared as described in Description 17; 250 mg, 0.76 mmol) in 1,2-dimethoxyethane (3 ml) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (189 mg, 0.91 mmol), tripotassium phosphate (321 mg, 1.51 mmol), and Pd(Ph3P)4 (52.5 mg, 0.05 mmol). The reaction was heated at 120° C. for one hour, cooled and the solvent removed in vacuo. The residue was redissolved in N,N-dimethylformamide (4 ml) and cesium carbonate (493 mg, 1.15 mmol) and 4-fluorobenzyl bromide (0.11 ml, 0.91 mmol) were added and the mixture heated at 40° C. for 3 hours. Water (10 ml) and ethyl acetate (15 ml) were added and the organic layer was separated and washed further with water (2×10 ml), dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (SiO2; (solute, 10% 7M NH3 in methanol/dichloromethane) yielded the title compound as a gum. 333 mg.

1. temperaturecooled
2. customthe solvent removed in vacuo
3. dissolutionThe residue was redissolved in N,N-dimethylformamide (4 ml)
4. temperaturethe mixture heated at 40° C. for 3 hours
5. customthe organic layer was separated
6. washwashed further with water (2×10 ml)
7. dry with materialdried (MgSO4)
8. customthe solvent removed in vacuo
9. customPurification by column chromatography (SiO2