Water → N-p-Benzeneacetonitrile menthanecarboxamide

Participants

Reaction Conditions

Reaction Steps

A 250 mL 3-neck flask was fitted with a condenser and a nitrogen inlet was charged with 10.00 g (0.0546 mol) of (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide, 0.522 g (0.0027 mol) copper (I) iodide, 13.26 g (0.0546 mol) of 4-(cyanomethyl)phenyl iodide, 23.18 g (0.109 mol) of potassium phosphate. The system was purged with nitrogen and a magnetic stir bar was added. After the addition of 170 mL of toluene, 3.42 g (0.190 mol) of water and 0.964 g (0.0109 mol) of N,N′-dimethylethylene diamine, the mixture was heated to 100° C. and stirred for 21 h under nitrogen. The crude reaction mixture was filtered through 50 g of silica gel (wet with 1:1 ethyl acetate/methylene chloride), and the bed was rinsed three times with 1:1 ethyl acetate/methylene chloride (150+75+75 mL). Concentration of the mixture in vacuo provided N-[4-(cyanomethyl)phenyl]-(1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide as a thick oil oil which was further purified by flash chromatography on silica gel eluting with mixtures of ethyl acetate and hexanes. The product has the following properties with the structure confirmed by obtaining an X-ray crystal structure of a sample crystallized from hexane/ethyl acetate.

Provenance & Evidence