Imidazole → (3S,4R)-3-[(R)-1-hydroxyethyl]-4-[(R)-1-methyl-3-allyloxycarbonyl-2-oxopropyl]-2-azetidinone

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of magnesium ethoxide (14.7 g) in tetrahydrofuran (250 ml) was added allyl hydrogen malonate (38.8 g) at 30° C. under nitrogen atmosphere. The resultant mixture was stirred at ambient temperature for 10 hours. To this mixture were added (3S,4R)-3-[(1R)-1-hydroxyethyl]-4-[(1R)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinone (24.7 g) and imidazole (8.8 g), and the mixture was allowed to heat to 60° C. for 1 hour. After evaporation of the solvent in vacuo, the residue was taken up into a mixture of ethyl acetate (300 ml) and brine (200 ml). After adjusting to pH 3.5 with concentrated hydrochloric acid at 5° C., the organic layer was separated and diluted with brine (200 ml). After adjusting to pH 8 with 30% aqueous potassium carbonate at 5° C., the organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (600 ml) eluting with a mixture of dichloromethane and acetone (19:1-1:1 v/v) to give allyl (4R)-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (19.46 g).

Provenance & Evidence