Reaktion #494780

Reaktionsgleichung

hydrochloric acid

HATU

lithium hydroxide

(1R,2S)-1-amino-2-vinyl-cyclopropane carboxylic acid ethyl ester hydrochloride

diisopropylethylamine

Compound 146

3-Oxo-2-oxa-bicyclo[2.2.1]heptane-5-carboxylic acid tert-butyl ester

→

title compound

Ausbeute 89.0%

(1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-hydroxy-cyclopentanecarboxylic acid tert-butyl ester

Ausbeute 89.0%

Lösungsmittel

dioxane water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeevaporated
2. 2
   workup.DISSOLUTIONThe crystalline residue was dissolved in DMF (5 mL)
3. 3
   Temperaturthe solution was cooled to 0° C
4. 4
   workup.STIRRINGthe mixture was stirred for 0.5 h at 0° C. and for an additional 2 h at room temperature
5. 5
   SonstigeThe mixture was then evaporated
6. 6
   Extraktionextracted with EtOAc
7. 7
   Waschenwashed with brine
8. 8
   Sonstigedried
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated
11. 11
    SonstigePurification by flash column chromatography (toluene/EtOAc 1:1)

Vorschrift

Compound 146 (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-vinyl-cyclopropane 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.

Quelle