869800-25-9

Upstream product

• 869800-23-7 (S)-2-[(2-chloro-ethyl)-(1-phenyl-ethyl)-amino]-acetonitrile 
• 204274-30-6 methyl (2R,1'S)-1-(1'-methyl)benzylazetidine-2-carboxylate 
• 6623-43-4 (S)-(-)-N-(2-hydroxyethyl)-α-methylbenzylamine 
• 2627-86-3 (S)-1-phenyl-ethylamine 
• 869800-22-6 (S)-2-[(2-hydroxy-ethyl)-(1-phenyl-ethyl)-amino]-acetonitrile 
• 869800-24-8 [1(1S),2S]-1-(1-phenyl-ethyl)-azetidine-2-carbonitrile 

Downstream Products

• 869800-24-8 [1(1S),2S]-1-(1-phenyl-ethyl)-azetidine-2-carbonitrile 
• 869800-26-0 (R)-1-((S)-1-Phenyl-ethyl)-azetidine-2-carboxylic acid; hydrochloride 
• 1047988-11-3 ethyl 1-((S)-1-phenylethyl)azetidine-2-carboxylate 
• 869800-26-0 (S)-1-((S)-1-Phenyl-ethyl)-azetidine-2-carboxylic acid; hydrochloride 

Relevant academic research and scientific papers

Synthesis of optically active 2-substituted azetidine-2-carbonitriles from chiral 1-arylethylamineviaα-alkylation ofN-borane complexes

The base-promoted α-alkylation ofN-((S)-1-arylethyl)azetidine-2-carbonitriles3viaformation of theirN-borane complexes4was investigated. For example, treatment of diastereomerically pure boraneN-((S)-1′-(4′′-methoxyphenyl)ethyl)azetidine-2-carbonitrile complex (1S,2S,1′S)-4bwith 1.2 equivalents of LDA at ?78 °C followed by 1.3 equivalents of benzyl bromide at ?78 °C and warming to room temperature produced α-benzylated (2S,1′S)-5bain 72% yield and (2R,1′S)-5bain 2% yield. A mechanism for this diastereoselective α-alkylation was proposed. Our method enables the production of optically active 2-substituted azetidine-2-carbonitriles, such as α-benzylated (S)-10aand (R)-10a, starting from commercially available (S)-(1-(4-methoxyphenyl)ethyl)amine.

Practical asymmetric preparation of azetidine-2-carboxylic acid

Facile and straightforward syntheses of both enantiomers of azetidine-2-carboxylic acid are described. The syntheses depart from inexpensive chemicals and allow for the production, in five to six steps, of practical quantities of each enantiomer. Synthetic highlights include the construction of the azetidine ring using an intramolecular alkylation and the use of optically active α-methylbenzylamine as chiral auxiliary.