Efficient synthesis of 2-aminoindane-2-carboxylic acid via dialkylation of nucleophilic glycine equivalent.
An efficient, easy to scale-up method for preparing 2-aminoindane-2-carboxylic acid via two-step alkylation of a Ni(II)-complex of glycine Schiff base with 2-[N-(alpha-picolyl)amino]benzophenone (PAAP) (2b) with o-dibromoxylylene (3) is reported. The first step, monoalkylation of 2b with 3, conducted under phase-transfer conditions, gave the corresponding complex 6 in excellent chemical yield (97.2%). Without any purification the intermediate 6 was cyclized under homogeneous conditions (DMF, NaO-t-Bu) to give the product 7 in high chemical yield (93.1%). Decomposition of prepared 7 afforded the target amino acid 2-aminoindane-2-carboxylic acid (1) in 97.9% yield, along with recovery of ligand 8, which was converted back to the starting glycine complex 2b. Operationally convenient experimental procedures, mild reaction conditions, as well as high chemical and volume yields render the method practical for preparing amino acid 1 and its analogues.
Ellis
Trevor K
TK
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA.
Hochla
Veronica M
VM
Soloshonok
Vadim A
VA
D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000032:analysis / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D005998:Glycine / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
C480478:2-aminoindane-2-carboxylic acid; D000596:Amino Acids; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D005998:Glycine