1601461-40-8

Upstream product

• 1001754-59-1 (±)-1-(tert-butoxycarbonyl)-3-fluoropyrrolidine-3-carboxylic acid 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1262410-84-3 ( R)-(-)-tert-butyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate 
• 1438852-72-2 (3R)-1-(tert-butoxycarbonyl)-3-fluoropyrrolidine-3-carboxylic acid 

Downstream Products

• 1601461-42-0 tert-butyl (3S)-3-fluoro-3-([((1R)-1-phenylethyl)amino]methyl)pyrrolidine-1-carboxylate 
• 1601461-44-2 tert-butyl (3S)-3-aminomethyl-3-fluoropyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

NOVEL COMPOUNDS

A compound of formula (I): wherein R represents H or F, or a salt thereof.

NOVEL COMPOUNDS

A compound of formula (I): being 4-(3-Fluoro-3-(2-(5, 6, 7, 8-tetrahydro-l, 8-naphthyridin-2-yl) ethyl) pyrrolidin-l-yl)-3-(3-(2-methoxyethoxy) phenyl) butanoic acid, or a salt thereof.

Determination of the absolute configuration of (+)- and (?)-N-CBZ-3-fluoropyrrolidine-3-methanol using vibrational circular dichroism and confirmation of stereochemistry by conversion to (R)-tert-butyl 3-fluoro-3-(((R)-1-phenylethyl)carbamoyl)pyrrolidine-1-carboxylate

Racemic N-CBZ-3-fluoropyrrolidine-3-methanol (±)-1 was resolved by preparative chiral HPLC. The absolute configuration of the enantiomers of 1 was identified by vibrational circular dichroism and confirmed by chemical synthesis, which involved exchanging the CBZ protecting group of (?)-1 with Boc, followed by oxidation with RuCl3, NaIO4, activation of the resulting acid with carbonyl diimidazole and reaction with (R)-α-methylbenzylamine to give (R)-tert-butyl 3-fluoro-3-(((R)-1-phenylethyl)carbamoyl) pyrrolidine-1-carboxylate 7. The latter was compared with authentic (S)-tert-butyl 3-fluoro-3-(((R)-1-phenylethyl)carbamoyl)pyrrolidine-1-carboxylate 6 and its diastereomer 7; the configuration of diastereomer 6 was obtained by an X-ray diffraction study. This established that the enantiomer (?)-1 had an (R)-configuration.

Convenient synthesis of enantiopure (R-) and (S-)-3-fluoro-3- aminomethylpyrrolidines

(R-)- and (S-)-3-fluoro-3-aminomethylpyrrolidines were synthesized from methyl α-fluoroacrylate in eight steps. α-Phenylethylamine was used as a chiral auxiliary to separate the racemic mixture. The overall synthesis yield was 31%.