344765-10-2

Upstream product

• 66399-75-5 (S)-2-benzylamino-3-phenyl-propionic acid methyl ester 
• 79-04-9 chloroacetyl chloride 
• 541-88-8 Chloroacetic anhydride 

Downstream Products

• 344765-38-4 4-carboxy-1,4-dibenzyl-2-azetidinone 
• 344765-23-7 1,4-dibenzyl-4-methoxycarbonyl-2-azetidinone 

Relevant academic research and scientific papers

Quaternary Ammonium-Supported Scavenger Reagents for Acids and Electrophiles

The present article describes how we devised new quaternary ammonium-supported quench reagents (TAMA-Cl and BAX-sulfate) for scavenging acids and excess electrophiles from crude reaction mixtures. TAMA-Cl is liquid at room temperature, but is very glutinous and has to be used in aqueous solution. It removes unchanged electrophiles very efficiently. An aqueous preparation of TAMA-Cl may be easily added in automated syntheses, and high-throughput phase-separation techniques shoud allow purification of scavening-containing reaction mixtures. However, workup with TAMA-Cl is more complex than simple filtration. Recognizing this major advantage of solid-phase syntheses, we designed BAX-sulfate, a highly crystalline scavenger reagent that allows reactions workup to be simplified to a single filtration and evaporation of solvent. BAX-sulfate reacts with electrophiles; quenches acids and precipitates quantitatively when diethyl ether is added. It even precipitates from methanol solutions. With BAX-sulfate the workup stage uses simple filtration to make crude separations.

Entry to new conformationally constrained amino acids. First synthesis of 3-unsubstituted 4-alkyl-4-carboxy-2-azetidinone derivatives via an intramolecular Nα-Cα-cyclization strategy

A systematic study on the base-assisted intramolecular alkylation of N-benzyl-N-chloroacetyl amino acid derivatives is described. This study resulted in the first concise and versatile route to the preparation of 3-unsubstituted 4-alkyl-4-carboxy-2-azetidinones, to be included into the scarce family of β-lactams with quaternary centers at the C4 position. Particularly noteworthy is that the intramolecular Nα-Cα-cyclization of Phe and Leu derivatives afforded the corresponding β-lactam derivatives with moderate enantioselectivity (up to 56%). It is suggested that, in these particular cases, the cyclization reaction proceeds by way of planar enolate intermediates, which possess dynamic chirality. The described sequence of reactions, that is compatible with commonly used protecting moieties for the α-carboxy group, cannot be applied to dipeptides, since the cyclization to the six-membered 2,5-diketopiperazine ring occurrs preferentially.