(R)-4-Propyldihydrofuran-2(3H)-one

Description

(R)-4-Propyldihydrofuran-2(3H)-one is the key intermediate in the diastereoselective synthesis of Brivaracetam, an active ingredient with antiepileptic properties belonging to the racetam family.

Chemical Properties

(R)-4-Propyldihydrofuran-2(3H)-one is a yellow oily liquid, slightly soluble in chloroform, methanol and ethanol. It needs to be stored at 2-8°C.

Uses

(R)-Dihydro-4-propyl-2(3H)-furanone, is building block used in various chemical synthesis.

Synthesis

Add a solution of H5IO6 (24.429 g, 107.17 mmol) in water (43 mL) to a solution of (R)-2-benzylpentyl acetate (1.180 g) in CCl4 (27 mL) and CH3CN (27 mL) at 0 °C. Add RuCl3·nH2O (0.222 g, 1.07 mmol) slowly to the mixture at 0 °C. Stir the resultant mixture vigorously for 20 hours at room temperature. Quench the reaction with Et2O (50 mL) at 0 °C. Stir the mixture for 30 minutes. Extract the mixture with Et2O (3 × 50 mL).
Wash the combined organic layers with brine (30 mL). Dry the combined organic layers over anhydrous Na2SO4. Filter the combined organic layers. Remove the solvent. Dissolve the oil in aqueous NaOH (1 mol L-1, 40 mL). Stir the resulting solution overnight at room temperature. Wash the solution with Et2O (30 mL). Acidify the solution with aqueous HCl (6 mol L-1, 15 mL) at 0 °C. Stir the mixture overnight at room temperature. Saturate the aqueous layer with NaCl. Extract the mixture with Et2O (5 × 40 mL). Wash the combined organic layers with water, saturated aqueous Na2S2O3 (30 mL) and brine (30 mL).
Dry the combined organic layers over anhydrous Na2SO4. Filter the combined organic layers. Remove the solvent. Purify the residue by column chromatography on silica gel (hexane/acetone = 3/1) and distillation (162-209 °C/36 mmHg).