反应详情

1-Propanephosphonic acid cyclic anhydride (1.752 mmol. 1.043 ml, 1115 mg) was added to a solution of (S)-tert-butyl 2-isopropylpiperazine-1-carboxylate (0.876 mmol, 200 mg), 4-amino-3-fluorobenzoic acid (0.876 mmol, 136 mg) and triethylamine (1.752 mmol, 0.244 ml, 177 mg) in dichloromethane and stirred at room temperature for 2 hours. After this time, ethyl acetate (100 mL) was then added to the reaction. The organic mixture was washed with saturated sodium hydrogen carbonate, water, dried over sodium sulphate and concentrated under vacuum. The residue was then dissolved in dichloromethane (5 ml) and trifluoroacetic acid (17.52 mmol, 1997 mg) added. The resultant solution was allowed to stand at room temperature overnight. The reaction was concentrated under vacuum and purified by strong cation exchange chromatography to give the title compound (200 mg) as a clear oil. MS (ESI) m/z 266.3 [M+H]+

1. washThe organic mixture was washed with saturated sodium hydrogen carbonate, water
2. dry with materialdried over sodium sulphate
3. concentrationconcentrated under vacuum
4. dissolutionThe residue was then dissolved in dichloromethane (5 ml)
5. waitto stand at room temperature overnight
6. concentrationThe reaction was concentrated under vacuum
7. custompurified by strong cation exchange chromatography