反应详情

温度

0 °C

Compound 34 (56 mg, 0.264 mmol) was dissolved in dioxane/water 1:1 (5 mL) and the mixture was cooled to 0° C. 1 M lithium hydroxide (0.52 mL, 0.520 mmol) was added and the mixture was stirred at 0° C. for 45 minutes, after which the mixture was neutralized with 1M hydrochloric acid and evaporated and coevaporated with toluene. The crystalline residue was dissolved in DMF (5 mL) and (1R,2S)-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester hydrochloride (60 mg, 0.313 mmol) and diisopropylethylamine (DIEA) (138 μL, 0.792 mmol) were added and the solution was cooled to 0° C. HATU (120 mg, 0.316 mmol) was added and the mixture was stirred for 0.5 h at 0° C. and for an additional 2 h at room temperature. The mixture was then evaporated and extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification by flash column chromatography (toluene/EtOAc 1:1) provided the title compound (86 mg, 89%) as a colourless oil. The afforded oil was crystallised from ethyl acetate-hexane.

1. customevaporated
2. dissolutionThe crystalline residue was dissolved in DMF (5 mL)
3. temperaturethe solution was cooled to 0° C
4. stirringthe mixture was stirred for 0.5 h at 0° C. and for an additional 2 h at room temperature
5. customThe mixture was then evaporated
6. extractionextracted with EtOAc
7. washwashed with brine
8. customdried
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by flash column chromatography (toluene/EtOAc 1:1)