Triethylamine → 2-[(7-Azido-1-oxoheptyl)amino]-2-[1-(S)-(naphthalen-2-yl)ethoxy]acetic acid, methyl ester

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Reaction Steps

A mixture of 4.4 g (26.1.10-3 mol) of 7-azidoheptanamide, 2.9 ml (29.2.10-3 mol) of methyl 2-hydroxy-2-methoxyacetate and 250 ml of dichloromethane is prepared and refluxed for 24 hours by means of a device which is such that the reflux condensate passes through a bed of 4 Å molecular sieves (about 30 g). After return to room temperature, the device for eliminating the methanol is removed and 2.29 ml (31.10-3 mol) of thionyl chloride are added to the reaction medium, which is then refluxed again for 1.75 h. The reaction mixture is subsequently concentrated under reduced pressure and then taken up with 50 ml of dichloromethane. A solution of 2.29 ml (31.10-3 mol) of triethylamine and 4.5 g (26.10-3 mol) of (S)-(-)-α-methyl-2-naphthalenemethanol [or 1-(S)-(naphthalen-2-yl)ethanol] in 50 ml of dichloromethane is added. The reaction mixture is stirred for 24 hours at room temperature and then washed successively with 100 ml of 1N hydrochloric acid and sodium chloride solution. After drying, the organic phase is concentrated under reduced pressure and the residue is purified by chromatography on silica gel using a hexane/2-propanol mixture (9/1 v/v) as the eluent to give 6.67 g of the expected product in the form of a colorless oil (yield=62%).

Provenance & Evidence