4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one

Description

4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one is a reagent used in organic synthesis, particularly for the introduction of the non-chiral (oxodioxolenyl)methyl carbamate group to active pharmaceutical ingredients (APIs) to afford the corresponding pro-drug.

Definition

4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one can be reacted with oxalyl chloride to afford (5-methyl-2-oxo-1,3-dioxol-4-yl) methylglyoxal chloride, which provides for an alternative approach to introduce the (oxodioxolenyl) methylcarbamate group.

The Uses of 4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one

4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one is used in preparation method of key intermediate of olmesartan medoxomil.

Preparation

At 20-25°C, 50 g of 4-chloromethyl-5-methyl-1,3-dioxol-2-one and 45 g of formic acid were added to 500 mL of acetonitrile. The reaction was cooled to 10-15°C followed by 95 g of triethylamine added. The mixture was heated to 60-65°C and stirred for approximately 5-6 h. The reaction system was subsequently cooled to 15-20°C, filtered, and washed with acetonitrile. Collecting filtrate, and the acetonitrile was removed under vacuum to concentrate the solution. The reaction system was again cooled to 25-30°C, and ethyl acetate and water were added. The mixture was then stirred for approximately 15-20 minutes at 25-30°C. Finally, 4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one was obtained after further purification.