反应详情

温度

130 °C

To a solution of phenylmethyl 5-bromo-4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]benzoate (may be prepared as described in Description 25; 730 mg, 1.430 mmol) in 1,2-dimethoxyethane (6 ml) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (357 mg, 1.72 mmol), tripotassium phosphate (607 mg, 2.86 mmol) and Pd(Ph3P)4 (99 mg, 0.09 mmol) followed by water (0.5 ml). The mixture was heated in a microwave at 130° C. for 90 minutes, cooled and the solvent removed in vacuo. Purification by column chromatography (SiO2; 1:1 ethyl acetate/cyclohexane to 10% 7M NH3 in methanol/dichloromethane) gave the intermediate. To a solution of this intermediate in tetrahydrofuran (4 ml) was added lithium hydroxide (103 mg, 4.29 mmol) and water (0.5 ml). The solution was stirred for 18 hours before neutralising with 2M hydrochloric acid (2.15 ml, 4.29 mmol). The solvent removed in vacuo to give the product as a solid. 603 mg.

1. temperaturecooled
2. customthe solvent removed in vacuo
3. customPurification by column chromatography (SiO2; 1:1 ethyl acetate/cyclohexane to 10% 7M NH3 in methanol/dichloromethane)
4. customgave the intermediate
5. customThe solvent removed in vacuo