An efficient asymmetric synthesis of (3S)-3-amino-1-(4-cyanophenyl)-2-oxopyrrolidine hydrochloride salt

Crystallization-Induced Diastereomer Transformations

“…After rac - 52 was stirred with this acid and 4 mol % of 3,5-dichlorosalicylaldehyde in wet ethyl acetate at 66 °C for 3.5 h, the diastereomerically pure ( R )- 52 (+)-DTTA salt could be isolated in high yield. A very similar CIDT was also reported by a Monsanto group 35 …”

“…A very similar CIDT was also reported by a Monsanto group. 117 Vogel et al recently reported a CIDT to prepare the metabolite (-)-53 of the anticonvulsant phenytoin. 118 In this case the equilibrating center is quaternary and equilibration cannot occur via proton transfer as in the previous examples.…”

Developing Processes for Crystallization-Induced Asymmetric Transformation

“…46 Searle researchers developed a CIDR process to resolve 35 using catalytic salicylaldehyde and (R)mandelic acid; a small amount of H 2 O was necessary for dynamic resolution. 47 Villani described CIDR of p-chlorophenylalanine methyl ester using salicylaldehyde, and the (R)-ester crystallized as the 2:1 salt with unnatural tartaric acid. 48 DSM has reported a CIDR process to resolve methionine amide using benzaldehyde and either L-or D-mandelic acid, 49 and Ciba-Geigy researchers developed a CIDR process for an aminobenzazepinone (the amide nitrogen of 24 was derivatized with a tert-butyl acetate group) using benzaldehyde.…”

“…GSK researchers used a catalytic amount of 3,5-dichlorosalicylaldehyde and a deficit of di- p -toluoyl- d -tartaric acid to prepare the chiral salt 34 . Searle researchers developed a CIDR process to resolve 35 using catalytic salicylaldehyde and ( R )-mandelic acid; a small amount of H 2 O was necessary for dynamic resolution . Villani described CIDR of p -chlorophenylalanine methyl ester using salicylaldehyde, and the ( R )-ester crystallized as the 2:1 salt with unnatural tartaric acid .…”