1-(3,4-Dimethoxyphenyl)cyclohexanecarbonitrile → [1-(3,4-Dimethoxyphenyl)cyclohexyl]methanamine

Participants

Reaction Conditions

Reaction Steps

(3,4-Dimethoxy-phenyl)-acetonitrile (5.00 g, 28.2 mmol) was dissolved in 60 mL of anhydrous tetrahydrofuran in a 250 mL round bottom flask. Sodium hydride (2.03 g, 84.6 mmol) was slowly added and the reaction mixture was warmed to 50-60° C. 1,4-Dichloropentane (4.78 g, 33.9 mmol) was then added and the reaction mixture was heated to reflux for 16 hours. The reaction mixture was cooled to room temperature and quenched with the slow addition of methanol. The reaction mixture was evaporated to dryness and purified by column chromatography on silica gel to yield a pale yellow oil (3.65 g, 14.9 mmol, 52.8%). The resulting 1-(3,4-dimethoxy-phenyl)-cyclohexanecarbonitrile (2.00 g, 8.15 mmol) was dissolved in dry ether (40 mL) and cooled to 0° C. under an atmosphere of nitrogen. Lithium aluminum hydride (8.15 mL, 1M in ether) was slowly added and the reaction mixture was allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was cooled to 0° C. and quenched with 0.34 mL water, 0.34 mL of 15% sodium hydroxide, and then an additional 1.4 mL of water. The reaction mixture was then filtered through celite, washed with water and a saturated aqueous sodium chloride solution. The filtrate was evaporated to dryness to give a colorless oil (1.91 g, 7.66 mmol, 94.0%). ESI-MS m/z calc. 249.2, found 250.2 (M+1)+. Retention time of 1.76 minutes.

Provenance & Evidence