N,N,N',N'-Tetramethylethylenediamine → benzyl (2S)-2-[(4-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}phenyl)(hydroxy)methyl]-2-methylpyrrolidine-1-carboxylate

Participants

Reaction Steps

423 mg of the compound [1-1] and 508 mg of N,N,N′,N′-tetramethylethylene diamine were dissolved in 22 mL of tetrahydrofuran, the temperature of the solution was kept at −78° C., and then 1.09 mL of n-butyl lithium (2.66 M hexane solution) was added thereto. After stirring at the same temperature for 1 hour to obtain the resultant white suspension, 2.2 mL of a tetrahydrofuran solution prepared by dissolving 384 mg of the compound [63-3] was added thereto, and the mixture was stirred at the same temperature for 1.5 hours. To the reaction mixture, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. Thereafter, the insolubles were filtered, and the filtrate was concentrated under reduced pressure to obtain benzyl (2S)-2-[(4-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}phenyl)(hydroxy)methyl]-2-methylpyrrolidine-1-carboxylate [634]. The compound [634] obtained was a mixture of two isomers, which was then purified by silica gel column chromatography (eluent: hexane/ethyl acetate=100/0 to 40/60) to obtain 199 mg of a low polarity compound (compound that eluted first under the above condition) [634a] (hereinafter, referred to as the compound [634a]) and 117 mg of a high polarity compound (compound that eluted afterwards under the above condition) [634b] (hereinafter, referred to as the compound [63-4b]). Here, the compound [634a] is a precursor of a compound [63], and the compound [634b] is a precursor of a compound [64] described later.

Provenance & Evidence