Enantiomers of all-cis-5-(4-bromophenyl)-4-tert-butoxycarbonyl-2-methoxycarbonylpyrrolidine: preparative HPLC separation and acylative kinetic resolution of the racemate

The fundamental possibility of acylative kinetic resolution of racemic heterocyclic amines was demonstrated by the example of all-cis-5-(4-bromophenyl)-4-tert-butoxycarbonyl-2-methoxycarbonylpyrrolidine. Individual enantiomers (ee >99%) were obtained in high yields via preparative chiral HPLC.

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(2R,4R,5S)-5-(4-Bromophenyl)-4-tert-butoxycarbonyl-2-methoxycarbonylpyrrolidineC17H22BrNO4[α]D20=-33.0 (c 1.0, C6H6)Source of chirality: Chiral HPLCAbsolute configuration: (2R,4R,5S)

N-Methyl-N-tosyl-(S)-phenylalanyl chlorideC17H18ClNO3S[α]D20=+45.3 (c 1.1, C6H6)Source of chirality: (S)-PhenylalanineAbsolute configuration: (2S)

(2R,4R,5S)-5-(4-Bromophenyl)-4-tert-butoxy-carbonyl-1-[(2′S)-2′-(6″-methoxynapht-2″-yl)propionyl]-2-methoxy-carbonylpyrrolidineC17H18ClNO3S[α]D20=-132 (c 1.0, C6H6)Source of chirality: (S)-NaproxenAbsolute configuration: (2′S,2R,4R,5S)

(2S,4S,5R)-5-(4-Bromophenyl)-4-tert-butoxycarbonyl-1-[(2′S)-N-phthaloylphenylalanyl]-2-methoxycarbonylpyrrolidineC17H18ClNO3S[α]D20=+52.4 (c 1.0, C6H6)Source of chirality: N-Phthaloyl-(S)-phenylalanineAbsolute configuration: (2′S,2S,4S,5R)

(2S,4S,5R)-5-(4-Bromophenyl)-4-tert-butoxycarbonyl-1-[(2′S)-N-phthaloylleucyl]-2-methoxycarbonylpyrrolidineC17H18ClNO3S[α]D20=+58.5 (c 1.0, C6H6)Source of chirality: N-Phthaloyl-(S)-leucineAbsolute configuration: (2′S,2S,4S,5R)