反应详情

温度

120 °C

To a solution of tert-butyl 4-(3-hydroxyphenyl)piperazine-1-carboxylate (D18) (143.18 mg, 0.514 mmole) in dimethylformamide (2 ml), potassium carbonate (71 mg, 0.514 mmol) and the reaction mixture was heated 2 h at 80° C. methyl 5-chloro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinate (D63) (150 mg, 0.467 mmol) in dimethylformamide (2 ml) was added dropwise and the resulting mixture stirred 21 h at 120° C. After cooling at room temperature, 1M NaOH (0.935 ml) was added and the mixture stirred 1 h at 120° C. After cooling the reaction mixture was extracted with diethylether (2×10 ml) and the aqueous was evaporated in vacuo. The residue was purified by SPE-Si cartridge (5 g) eluting with a mixture dichloromethane/methanol from 100/0 to 80/20. Collected fractions, after solvent evaporation afforde the title compound (D110) (155 mg)

1. additionwas added dropwise
2. temperatureAfter cooling at room temperature
3. stirringthe mixture stirred 1 h at 120° C
4. temperatureAfter cooling the reaction mixture
5. extractionwas extracted with diethylether (2×10 ml)
6. customthe aqueous was evaporated in vacuo
7. customThe residue was purified by SPE-Si cartridge (5 g)
8. washeluting with a mixture dichloromethane/methanol from 100/0 to 80/20
9. customCollected fractions, after solvent evaporation afforde the title compound (D110) (155 mg)