(S)-Ethyl 2-(1-phenylethylamino)cyclohex-1-enecarboxylate → (1R,2S)-Ethyl 2-((S)-1-phenylethylamino)cyclohexanecarboxylate

Participants

Reaction Steps

In an additional embodiment, (1S,2S)-2-[(S)-1-phenylethyl amino]cyclohexyl)methanol (11) is produced from a starting material comprising ethyl 2-oxocyclohexane carboxylate (6). This embodiment comprises reacting ethyl 2-oxocyclohexane carboxylate (6) with (S)-(−)-1-phenylethylamine (7) in the presence of a catalyst, ytterbium trifluoromethanesulfonate, and heptane to produce (S)-Ethyl 2-(1-phenylethylamino)cyclohex-1-enecarboxylate (8). The next step is reduction of the amine (8) with sodium acetoxyborohydride in the presence of a acetonitrile produce (1R,2S)-Ethyl 2-((S)-1-phenylethylamino)cyclohexanecarboxylate (9), as illustrated in FIG. 1. The production of the cis-cyclohexane derivative (9) is followed by epimerization of the chiral center adjacent to the ethyl ester functionality using sodium t-butoxide to afford trans-cyclohexane derivative (10) as a major diastereomer. Reduction of the ester functionality in compound (10), using lithium borohydride yields (1S,2S)-2-[(S)-1-phenylethyl amino]cyclohexyl)methanol (11) in good overall yield, which is subsequently purified by chromatography.

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