Ammonium Chloride → Benzyl 1-benzyl-3-(2-(tert-butoxy)-2-oxoethyl)-4-methylpyrrolidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

Benzyl (3RS,4SR)-1-benzyl-4-methylpyrrolidine-3-carboxylate obtained in Example 1f (30 g, 97.4 mmol) was dissolved in tetrahydrofuran (300 ml), which was cooled to −70° C. with stirring under nitrogen. A 1.11M lithium diisopropylamide/n-hexane-tetrahydrofuran solution (105 ml, 116 mmol) was added dropwise over 20 minutes so that the internal temperature did not exceed −64.3° C. The mixture was stirred at −70° C. for 1 hour, and tetrahydrofuran (30 ml) and tert-butyl bromoacetate (26.6 g, 136 mmol) were then added dropwise over 10 minutes so that the internal temperature did not exceed −60° C. The reaction mixture was stirred at −70° C. for further one hour, and a saturated aqueous ammonium chloride solution was then added to the reaction mixture. Immediately thereafter, the reaction mixture was diluted with water and ethyl acetate was added. The organic layer was washed with brine and a 5 N aqueous hydrochloric acid solution, and then dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane). The residue was further purified by NH silica gel column chromatography (elution solvent: heptane/ethyl acetate=98/2) to give the title compound (6 g, yield: 14.5%).

Provenance & Evidence