反应详情

温度

100 °C

To a solution of [1-(hydroxymethyl)cyclopropyl]acetonitrile (1 eq.) (prepared according to the procedure described in WO2005/105749 Example 2/Step 4) in ethanol (0.1 M) was added 8 N aqueous KOH solution (18 eq.). The reaction was heated to 100° C. and stirred for 18 h. After cooling to rt temperature, ethanol was removed in vacuo. The resulting aqueous solution was diluted with EtOAc and cooled in ice water bath. Concentrated HCl was added slowly with stirring over 15 min, keeping the temperature of the reaction below 10° C. After the reaction has reached pH<1, the aqueous layer was extracted by EtOAc. The combined organic extracts were dried over MgSO4 and filtered. The EtOAc solution was cooled down to 0° C., and a solution of diazomethane in ether was added until a faint yellow color persisted. The reaction was allowed to stir for an additional 10 min before concentrated in vacuo. The crude product was purified on flash column chromatography (SiO2, 40% EtOAc in Hex) to afford the title compound as a liquid.

1. customwas removed in vacuo
2. additionThe resulting aqueous solution was diluted with EtOAc
3. temperaturecooled in ice water bath
4. additionConcentrated HCl was added slowly
5. stirringwith stirring over 15 min
6. customthe temperature of the reaction below 10° C
7. extractionthe aqueous layer was extracted by EtOAc
8. dry with materialThe combined organic extracts were dried over MgSO4
9. filtrationfiltered
10. temperatureThe EtOAc solution was cooled down to 0° C.
11. additiona solution of diazomethane in ether was added until a faint yellow color
12. stirringto stir for an additional 10 min
13. concentrationbefore concentrated in vacuo
14. customThe crude product was purified on flash column chromatography (SiO2, 40% EtOAc in Hex)