Hydrochloric Acid → (3R,5S)-1-allyloxycarbonyl-3-hydroxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine

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Reaction Steps

Concentrated hydrochloric acid (0.85 ml) is added dropwise to a solution of 899 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine in 20 ml of dry acetonitrile under ice cooling, and the mixture is stirred at that temperature for 20 min. The reaction solution is diluted with 50 ml of ethyl acetate, water is added thereto, and the mixture is rendered weakly alkaline by addition of a saturated aqueous sodium hydrogencarbonate solution. The mixture is then extracted three times with ethyl acetate, and the organic layer is washed twice with saturated saline, dried over anhydrous magnesium sulfate and filtered. The solvent is removed by evaporation under reduced pressure to give a crude product of (3R,5S)-1-allyloxycarbonyl-3-hydroxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine. Triethylamine (0.46 ml) and 0.24 ml of methanesulfonyl chloride are successively added to a solution of this compound in 20 ml of THF, and the mixture is stirred under an argon stream at −14° C. for 50 min. Water is added to the reaction solution, and the mixture is extracted four times with ethyl acetate. The organic layer is washed once with saturated saline, dried over anhydrous magnesium sulfate and filtered, and the solvent is removed by evaporation under reduced pressure to give a crude product which is then purified by column chromatography on silica gel (ethyl acetate:methanol=9:1) to give 472.6 mg of (3R,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]-3-methanesulfonyloxypyrrolidine (a diastereomer mixture) as a yellow viscous material.

Provenance & Evidence