Triphosgene → 2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-2-oxo-6-(5-oxo-4,5-dihydro-tetrazol-1-yl)-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{2-[6-amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester (173 mg in 5 mL dry methylene chloride) at 0° C. was added triphosgene (36 mg) followed by 0.073 mL of pyridine and the mixture stirred for 2 hour at 0° C. At this time the reaction was quenched by the addition water, washed with brine, dried over sodium sulfate and concentrated in vacuo to give the crude isocyante. This was solvated in 2 mL methylene chloride and added by cannula to a freshly prepared solution of aluminum azide (0.6 mmols in 5 mL tetrahydrofuran) and the resulting mixture heated to reflux on an oil bath. After 20 hours, the mixture was added to 10 mL of an iced, 1M potassium tartarate solution and stirred for 20 minutes. This was then diluted with water and extracted with ethyl acetate. The organic portion was washed successively with 1 M potassium tartarate, saturated ammonium chloride, water and brine, then dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (chloroform:10% acetic acid in methanol, 97:3) gave the title compound (160 mg).

Provenance & Evidence