Acetic Acid → (1R,2S)-Ethyl 2-((S)-1-phenylethylamino)cyclohexanecarboxylate

Participants

Reaction Conditions

Reaction Steps

Acetic acid (1.0 L) was added to a reactor followed by sodium borohydride (100 g) with cooling between 16-30° C. under nitrogen in NLT 1 hour and mixed for NLT 30 minutes. Acetonitrile (500 mL) was added and mixed for NLT 30 minutes, and the cooled to below 5° C. A solution of (S)-ethyl 2-(1-phenylethylamino)cyclohex-1-enecarboxylate (8, 269 g) dissolved in acetonitrile (250 mL) was added in NLT 30 minutes, while maintaining the temperature between 2-8° C. and then the reaction mixture was warmed to 22° C., and mixed for NLT 4 hours. The mixture was cooled below 5° C. and quenched with 1.77 L of 25% aqueous sodium hydroxide solution, water (1.3 L) and heptanes (0.75 L) and the pH was adjusted pH to ˜8.0. The organic layer was separated and the aqueous layer was extracted with heptanes (2×0.75 L), and then the combined heptane layers were washed with water (2×0.75 L) and 3.5 M aqueous sodium chloride solution (0.75 L). The heptane solution was then dried using anhydrous magnesium sulfate and concentrated under vacuum to afford 243.9 g of (1R,2S)-Ethyl 2-((S)-1-phenylethylamino)cyclohexanecarboxylate (9) as the major isomer.

Provenance & Evidence