4,4-DIMETHYLCYCLOHEXYLAMINE

Synthesis

The general procedure for the synthesis of 4,4-dimethylcyclohexylamine from 4,4-dimethylcyclohexanone oxime was as follows: 4,4-dimethylcyclohexanone oxime (10 g, 71 mmol, 1 equiv.) was dissolved in ethanol (100 mL) and Raney Ni catalyst (1 g, 10% w/w) was added. The reaction mixture was stirred under hydrogen atmosphere (50 psi) for 4 hours. Upon completion of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad. Hydrochloric acid (1 M in H2O, 100 mL, 100 mmol, 1.4 eq.) was added to the filtrate and the resulting precipitate was collected by filtration and dissolved in water. The aqueous phase was washed with ether and alkalized to a strong base with potassium hydroxide pellets and subsequently extracted twice with dichloromethane. The organic phases were combined, dried over magnesium sulfate and concentrated in vacuum to afford 4,4-dimethylcyclohexylamine (8 g, 89% yield) as a clear oil, which can be used in the next reaction without further purification.

References

[1] Patent: WO2004/50619, 2004, A1. Location in patent: Page 78-79
[2] Patent: WO2014/37900, 2014, A1. Location in patent: Page/Page column 33
[3] Journal of medicinal chemistry, 1971, vol. 14, # 17, p. 600 - 614
[4] Journal of the Chemical Society [Section] B: Physical Organic, 1971, p. 1047 - 1050