Ethyl-4-aminocyclohexane carboxylate

Some workers allow the amine and carbonyl compound to stand together some time before hydrogenation (i,59), but this procedure is not always necessary nor even desirable (ii). The delay technique is illustrated by reductive alkylation of ethyl-4-aminocyclohexane carboxylate (4) with benzaldehyde to S, a route that permitted an important improvement in the production of isoquinuclidine (8) (59). 

The H-NMR spectrum of pure as-4-aminocyclohexane carboxylic acid ethyl ester is seen in Figure 1. Signals with chemical shift at 5=1.2-1.3 ppm can be assigned to the protons of the methyl group, whereas the signals of the -CH2- protons... 

Figure 1 NMR spectrum of as-4-aminocyclohexane carboxylic acid ethyl ester.

The H-NMR spectrum of lra/3s-4-aminocyclohexane carboxylic acid ethyl ester is enriched in a mixture containing ca. 10 % of the cis isomer is seen in Figure 3. The signals belonging to the protons next to the ester and amino groups in the trans isomer appeared at chemical shifts of 5=2.20 ppm and 5=2.65 ppm, respectively. The intensity of signals in the NMR spectra allows estimating the ratio of stereoisomers. 

Derivatives of mono- and dicarboxylic acids are another important source of ortho- and mefa-aminocyclohexane carboxylic acids, but not the para-derivatives. Anhydride 7.181 was converted to the amide, then to 7.777 (c/s-2-aminocyclohex-ane-1-carboxylic acid) via a Hofmann reaction,12 and finally to cis- ethyl 2-amino-... 

A different approach using alkene derivatives involved allylic substitution reactions. Ethyl cyclohex-3-en-l-carboxylate (7.51) reacted with N-bromosuccin-imide to give 7.52.26 This allowed reaction with potassium phthalimide to give 7.53 in an overall yield of 41%. Catalytic hydrogenation and treatment with methylamine led to ds-3-aminocyclohexane-l-carboxylic acid, 7.22.26... 

Another approach using ketones converted cyclohexanone to 1-cyano-l-cyclohexene (7.150). Conjugate addition of ammonia and esterification led to trans-ethyl 2-aminocyclohexane-l-carboxylate, 7.151. 

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