Sodium hydride → (3S,4S)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-4-[(1R)-1-carboxyethyl]-1-(allyloxycarbonylmethyl)-2-azetidinone

Participants

Reaction Conditions

Reaction Steps

(3S,4S)-3-[(1R)-1-t-Butyldimethylsilyloxyethyl]-4-[(1R)-1-carboxyethyl]-2-azetidinone (6 g) is dissolved in tetrahydrofuran (250 ml), and thereto is added 60% sodium hydride (0.796 g) at 10° C., and the mixture is stirred at 20° C. for 20 minutes. To the mixture is added t-butyldimethylsilyl chloride (3 g) at 10° C., and the mixture is stirred for 10 minutes, and concentrated under reduced pressure to the quarter volume thereof. The concentrated mixture is stirred at 20° C. for 20 minutes, and thereto is added a mixture of bromoacetic acid allyl ester (3.56 g) and tetrahydrofuran (190 ml), and further added thereto dropwise 1M solution (20 ml) of sodium bis(trimethylsilyl)amide in tetrahydrofuran at -50° C. The mixture is warmed to 20° C. over a period of 30 minutes, and concentrated under reduced pressure to a quarter volume thereof. The concentrated mixture is stirred at 20° C. for 2 hours, and thereto is added tetrahydrofuran (190 ml), and further added dropwise a solution of potassium carbonate (2.8 g) in water (40 ml) at 10° C. The mixture is stirred at 20° C. for 15 minutes. To the mixture is added diluted hydrochloric acid [hydrochloric acid (4.2 g) in water (8 ml)] at 10° C., and thereto is added 1N hydrochloric acid (18 ml) under ice-cooling. The mixture is allowed to stand, and the organic layer is collected. The aqueous layer is extracted with chloroform, and the organic layers are combined, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform→chloroform:methanol=98:2) to give (3S,4S)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-4-[(1R)-1-carboxyethyl]-1-(allyloxycarbonylmethyl)-2-azetidinone (5.7 g) as oil.

Provenance & Evidence