4-Bromopyridinium chloride → 1-{(2S,4R)-1-benzyl-4-(t-butyl-dimethylsilyloxy)pyrrolidin-2-yl}-1-(4-pyridyl)methanol

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Reaction Steps

A solution of 4-bromopyridine hydrochloride (18.57 g) in ethyl ether (50 ml) and water (50 ml) was neutralized with sodium hydrogen carbonate in water (50 ml). After stirring for 10 minutes, the mixture was extracted three times with ethyl ether. The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure to give a residue. To a solution of the residue in ethyl ether (300 ml) was added n-butyllithium (1.68N solution in n-hexane) (63 ml) under -60° C. After the addition, the mixture was stirred for 30 minutes at -78° C. Then (2S,4R)-1-benzyl-4-(t-butyldimethylsilyloxy)-2-formylpyrrolidine (30.52 g) was added dropwise to the mixture under -60° C. After the addition, the mixture was stirred at -70° C. for 30 minutes and then warmed to room temperature. The raction mixture was quenched with water and extracted three times with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was column chromatographed on silica gel eluting with ethyl acetate:n-hexane=3:7 to 1:1) to give 1-{(2S,4R)-1-benzyl-4-(t-butyl-dimethylsilyloxy)pyrrolidin-2-yl}-1-(4-pyridyl)methanol (14.68 g).

Provenance & Evidence