反应详情

温度

55 °C

A mixture of 470 mg (1.19 mmole) of (S)-1-[N-(3,5-dichlorophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid (from Step E above), 393 mg (1.79 mmole) of N,N-di-n-pentylcarbamoyl chloride (from Example 1, Step C-2) and 578 mg (4.17 mmole) of triethylamine in 15 mL of THF and 8 mL of water was stirred at 55° C. for 24 hours. The mixture was cooled and treated with 16 mL of 0.5N aqueous hydrochloric acid, and the aqueous layer was extracted with 3×55 mL of ethyl acetate. The combined organic extracts piperazine-2-carboxylic acid (from Step E above), 393 mg (1.79 mmole) of N,N-di-n-pentylcarbamoyl chloride (from Example 1, Step C-2) and 578 mg (4.17 mmole) of triethylamine in 15 mL of THF and 8 mL of water was stirred at 55° C. for 24 hours. The mixture was cooled and treated with 16 mL of 0.5N aqueous hydrochloric acid, and the aqueous layer was extracted with 3×55 mL of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on 120 g of silica eluting with 1 L of 100:3 methylene chloride:methanol then 1 L of 100:4.5:0.15 methylene chloride:methanol: acetic acid to give 374 mg (54%) of an oil.

1. temperatureThe mixture was cooled
2. extractionthe aqueous layer was extracted with 3×55 mL of ethyl acetate
3. temperatureThe mixture was cooled
4. extractionthe aqueous layer was extracted with 3×55 mL of ethyl acetate
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography on 120 g of silica eluting with 1 L of 100:3 methylene chloride