Cyclobutanecarboxylic acid, 3-hydroxy-, methyl ester

695-95-4

4934-99-0

General procedure for the synthesis of methyl 3-hydroxycyclobutanecarboxylate from methyl 3-carbonyl-cyclobutanecarboxylate: Methyl 3-carbonyl-cyclobutanecarboxylate (307.5 g, 2.4 mol, 1.0 eq.) was dissolved in 3 L of tetrahydrofuran and the solution was cooled down to -78 to -60 °C. Subsequently, 3.5 L of tetrahydrofuran solution of lithium hydrogenated tri-tert-butoxyaluminum (915.4 g, 3.6 mol, 1.5 eq.) was added slowly and dropwise. After 3 hours of reaction, the completion of the reaction was confirmed by TLC. Then, 1 L of 2.5 mol/L hydrochloric acid was added dropwise to terminate the reaction and the pH of the reaction solution was adjusted to about 6 while the temperature was controlled at about 0 °C. The reaction mixture was diluted by adding 3 L of ethyl acetate and stirred for 30 minutes. The reaction mixture was filtered through diatomaceous earth and the filter cake was washed three times with ethyl acetate. The filtrate was separated and the aqueous phase was extracted with ethyl acetate. All organic phases were combined and concentrated by drying to give a yellow liquid methyl cis-3-hydroxycyclobutanecarboxylate (273.3 g, 2.1 mol) in 88% yield and 95% purity.