Triethylamine → (-)-2-(2,4-Dimethoxyphenyl)heptyl cyanide

Participants

Reaction Steps

0.68 ml (8.79 mmol) of methanesulfonyl chloride was added to a solution of 2.01 g (7.97 mmol) of (-)-2-(2,4-dimethoxyphenyl)heptanol [prepared as described in step (i) above] in 20 ml of methylene chloride, and then 1.3 ml (9.33 mmol) of triethylamine were added dropwise to the resulting mixture over a period of 2 minutes, whilst ice-cooling. The resulting mixture was then stirred at the same temperature for 15 minutes, after which it was mixed with water and then extracted with diethyl ether. The extract was washed with 2 N aqueous hydrochloric acid, with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in 10 ml of dimethylformamide, and to the resulting solution were added 611 mg (12.4 mmol) of sodium cyanide and 0.80 ml (4.0 mmol) of 15-crown-5. The resulting mixture was then stirred at 50° C. for 1 hour and then at 100° C. for 1 hour. At the end of this time, the reaction mixture was cooled to room temperature, after which it was mixed with water and then extracted with diethyl ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through 150 g of silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane ranging from 1:10 to 1:5 by volume as the eluent, to give fractions containing a pure compound. Fractions containing impure products were repeatedly subjected to column chromatography under the same conditions as above. A total of 1.58 g (yield 75%) of the title nitrile derivative was obtained as an oily substance.

Provenance & Evidence