Ammonium Chloride → allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate

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Reaction Steps

A 2 M methylmagnesium iodide/diethyl ether solution (1.30 ml) is diluted with 10 ml of anhydrous THF, and a solution of 650 mg of 7-iodoimidazo[5,1-b]thiazole in 10 ml of anhydrous THF is added dropwise to the diluted solution in an argon atmosphere over a period of 4 min. The mixture is stirred in this state at room temperature for additional 30 min. The internal temperature is lowered to −48° C., and the solution is added dropwise to a solution of 1.003 g of allyl(1R,5S,6S)-2-((3S,5S)-1-allyloxycarbonyl-5-formylpyrrolidin-3-yl)thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate in 10 ml of anhydrous THF over a period of 5 min. The mixture is stirred in this state at −48 to −40° C. for 40 min, and the temperature is then raised to −25° C. over a period of 50 min. Semi-saturated aqueous ammonium chloride (50 ml) is added thereto, the mixture is extracted with 90 ml of ethyl acetate, and the organic layer is dried over anhydrous magnesium sulfate, followed by filtration and the removal of the solvent by evaporation to give a yellow viscous material. This viscous material is successively purified by column chromatography on Sephadex LH-20 (dichloromethane:methanol=1:1) and on silica gel (toluene:ethyl acetate=1:9) to give 491.3 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate (a diastereomer mixture) as a yellow amorphous material.

Provenance & Evidence