反应详情

To a mixture of (2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]acrylic acid (35.0 g), acetonitrile (245 mL) and dimethylformamide (0.175 mL) was added thionyl chloride (11.4 mL) at 40-45° C. and the mixture was stirred for 1 hr. Then diethyl 4-aminobenzylphosphonate (36.3 g) was added at 5° C. and diisopropylethylamine (61.9 mL) was further added dropwise. The mixture was stirred at room temperature for 1 hr. A 1N aqueous sodium hydroxide solution (140 mL) was added to neutralize the reaction mixture and water (472.5 mL) was further added. The mixture was stirred at room temperature for 1 hr. The precipitated crystals were collected by filtration and washed with 30% acetonitrile to give diethyl [4-({(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]prop-2-enoyl}amino)benzyl]phosphonate (61.5 g, yield 92%).

1. stirringThe mixture was stirred at room temperature for 1 hr
2. additionwas further added
3. stirringThe mixture was stirred at room temperature for 1 hr
4. filtrationThe precipitated crystals were collected by filtration
5. washwashed with 30% acetonitrile