Acetic Acid → 1-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a suspension of potassium tert-butoxide (3.14 g, 28 mmol) in THF (130 ml) heated at 60° C. was added tert-butyl (3S)-3-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino]-4-(methoxymethoxy)butanoate (5.24 g, 14 mmol) in THF (50 ml) and the mixture was stirred for 5 minutes. After cooled to 0° C. the reaction mixture was poured into diluted hydrochloric acid (after confirming that pH was about 3), a saturated aqueous sodium chloride solution was added thereto and the mixture was extracted three times with ethyl acetate. The organic layer was washed with water, then a saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed in vacuo. To a solution of the residue (4.17 g) in methanol (100 ml) were added acetic acid (1.45 ml, 25 mmol) and sodium cyanoborohydride (1.06 g, 17 mmol) and the mixture was stirred at room temperature for 30 minutes. The solvent was removed in vacuo. The residue was purified with silica gel (60 g) chromatography (hexane/ethyl acetate=2/1→1/1) to give 1-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylate (1.47 g, 30%).

Provenance & Evidence