反应详情

温度

55 °C

A mixture of 220 mg (0.53 mmole) of 1-[N-(3,5-dimethylphenyl)-N-phenylcarbamoyl]piperazine-2-(S)-carboxylic acid acetate salt (from Step E above), 175 mg (0.80 mmole) of N,N-di-n-pentylcarbamoyl chloride and 188 mg (1.86 mmole) of triethylamine in 6 mL of THF and 3 mL of water was stirred at 55° C. for 72 hours. To the mixture was added an additional 6 mL of THF, 175 mg of N,N-di-n-pentylcarbamoyl chloride, and 187 mg of triethylamine and the mixture again heated at 55° C. for 48 hours. To the mixture was added an additional 120 mg N,N-di-n-pentylcarbamoyl chloride and the reaction mixture heated for an additional 24 hours. The mixture was cooled and was partitioned between 16 mL of 0.5N aqueous HCl and 30 mL of EtOAc. The layers were separated and the aqueous layer extracted with 2×40 mL of EtOAc. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on 68 g of silica gel eluting with 100:4:0.1 CH2Cl2 :MeOH:HOAc to give 194 mg (68%) of an oil.

1. temperaturethe mixture again heated at 55° C. for 48 hours
2. temperaturethe reaction mixture heated for an additional 24 hours
3. temperatureThe mixture was cooled
4. customwas partitioned between 16 mL of 0.5N aqueous HCl and 30 mL of EtOAc
5. customThe layers were separated
6. extractionthe aqueous layer extracted with 2×40 mL of EtOAc
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by flash chromatography on 68 g of silica gel eluting with 100:4:0.1 CH2Cl2