Tri-o-tolylphosphine → methyl (R)-alpha-t-butoxycarbonylamino-7-chloro-3-diethylphosphonomethyl-6-methyl-2-quinolinepropionate

Participants

Reaction Steps

A solution of N-t-butoxycarbonyl-3-iodo-D-alanine methyl ester (0.81 g, 2.46 mmol) in dry toluene (12 ml) and dry dimethylacetamide (0.8 ml) was added to a nitrogen purged flask charged with zink-copper couple (0.32 g, 4.92 mmol). The mixture was treated in an ultrasonic bath for 1 h until no starting material remained (as judged by TLC). A mixture of PdCl2 (23 mg, 0.13 mmol) and tri-o-tolylphosphine (79 mg, 0.26 mmol) was added followed by 2-bromo-7-chloro-3-diethylphosphonomethyl-6-methylquinoline (0.5 g, 1.23 mmol) and sonication was continued for 3 hours at 50°-60° C. After cooling the reaction mixture was diluted with ethyl acetate, extracted with saturated sodium hydrogen carbonate solution, dried over MgSO4 and evaporated. The crude product was subjected to chromatography on silica gel with ethyl acetate as eluant to yield 0.49 g of methyl (R)-α-t-butoxycarbonylamino-7-chloro-3-diethylphosphonomethyl-6-methyl-2-quinolinepropionate.

Provenance & Evidence