Diethyl Ether → HCID 20080505, compound

Participants

Reaction Conditions

Reaction Steps

14.4 g of 7-cyanooctanoic acid dicyclohexylamine salt are added to a mixture of 45 cm3 of a molar solution of sodium hydrogen sulphate and 100 cm3 of diethyl ether. The mixture is stirred for 15 minutes at 20° C. and the organic phase is then separated. The latter is dried over magnesium sulphate and filtered and the solvent is evaporated off under reduced pressure. The residue, treated with 24.6 g of thionyl chloride is heated to 50° C. for 3 hours. The mixture is evaporated under reduced pressure. The residual oil is dissolved in 10 cm3 of dichloromethane, and the solution obtained is added to a suspension, stirred and cooled to 5° C., of 12.1 g of 2-amino-1,2-bis(4-methoxyphenyl)ethanone hydrochloride in 50 cm3 of dichloromethane containing 7.8 g of pyridine. The mixture is stirred for 20 hours at room temperature, 40 cm3 of water are then added and the organic phase is separated after settling has taken place and washed with 20 cm3 of normal hydrochloric acid and with water (3 times 20 cm3). The organic phase is dried over magnesium sulphate and filtered and the solvent is evaporated off under reduced pressure. The residue is chromatographed on a column 2.8 cm in diameter containing 100 g of silica gel (50 to 200μ). The column is eluted, collecting 200 cm3 fractions, with 4 liters of a diisopropyl ether/ethyl acetate (80:20 by volume) mixture. The fractions emerging at between 0.6 liter and 4 liters are concentrated under reduced pressure (0.2 kPa). 13.9 g (83%) of (RS)-1,2-bis(4-methoxyphenyl)-2-(7-cyanooctanamido)ethanone are obtained in the form of a yellowish oil, which is used directly in the subsequent reaction.

Provenance & Evidence