Water → benzyl (2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-isopropylpyrrolidine-1-carboxylate

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Reaction Steps

To a solution (10 mL) of ethyl (3S,4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate (700 mg) in tetrahydrofuran were added 2,6-lutidine (0.504 mL) and tert-butyldimethylsilane trifluoromethanesulfonate (0.596 mL), and the mixture was stirred at room temperature for 30 min. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the residue in tetrahydrofuran (5 mL)-ethanol (1 mL) was added lithium borohydride (94 mg), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution (10 mL) of the residue in tetrahydrofuran were added triethylamine (0.602 mL) and methanesulfonyl chloride (0.25 mL), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL), potassium tert-butoxide (363 mg) was added thereto under ice-cooling, and the mixture was stirred at room temperature for 18 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with 0.1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→5:1) to give the title compound (yield: 441 mg) as a pale-yellow oil.

Provenance & Evidence