627101-16-0

Upstream product

• 1611481-16-3 (2R,4R)-methyl 4-azido-1-benzylpyrrolidine-2-carboxylate 
• 114676-54-9 (2R,4R)-1-benzyl-2-carbomethoxy-4-<(methylsulfonyl)oxy>pyrrolidine 
• 178962-09-9 methyl (2R,4S)-4-hydroxypyrrolidine-2-carboxylate 
• 3398-22-9 trans-4-hydroxyproline 
• 627101-01-3 ethyl (2R,4S)-1-benzyl-4-(4-methylphenylsulfonyloxy)prolinate 
• 627100-99-6 ethyl (2R,4S)-1-benzyl-4-hydroxyprolinate 
• 627101-12-6 ethyl (2R,4R)-4-azido-1-benzylprolinate 

Downstream Products

• 1611481-18-5 tert-butyl (3R,5R)-1-benzyl-5-(hydroxymethyl)pyrrolidin-3-ylcarbamate 
• 1611488-11-9 (R)-N-(5,5-difluoropiperidin-3-yl)benzamide 
• 1611481-20-9 tert-butyl ((3S,5R)-1-benzyl-5-hydroxypiperidin-3-yl)carbamate 
• 1611481-21-0 tert-butyl (3R,5S)-5-hydroxypiperidin-3-ylcarbamate 
• 1611481-26-5 (R)-(5-amino-3,3-difluoropiperidin-1-yl)(phenyl)methanone 

Relevant academic research and scientific papers

Enantioselective synthesis and physicochemical properties of libraries of 3-amino- and 3-amidofluoropiperidines

The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pK a due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H+ and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pK a between cis- and trans-3-amino-5-fluoropiperidines.

Ex-chiral pool synthesis and receptor binding studies of 4-substituted prolinol derivatives

Starting from natural 4-hydroxyproline, preparation of the four possible stereoisomers of 4-amino- and 4-aminomethyl-substituted prolinol derivatives, respectively, was accomplished by chemo- and regioselective functional group transformations at the 2- and 4-positions of the pyrrolidine moiety. These building blocks were used as valuable precursors for the preparation of new methoxybenzamide derivatives. Dopamine and serotonin binding studies involving the subtypes D1, D2long, D2short, D3 and D4 as well as 5-HT1A and 5-HT2, respectively, displayed interesting structure activity relationships, especially with respect to the absolute and relative configuration of the test compounds. As a complement to the D3 receptor preferring aminomethylpyrrolidine FAUC 21, the (2R,4R)-aminoprolinol derivative ent-24 (FAUC 65) preferentially recognizing the D4 subtype was developed.