Ethanol → (1-Hydroxymethylcyclopropyl)acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence