Acetic Acid → ((1S,2S)-2-((S)-1-phenylethylamino)cyclohexyl)methanol

Participants

Reaction Conditions

Reaction Steps

Tetrahydrofuran (1.9 L) was charged to a reactor and cooled to 15° C. and lithium borohydride (52.8 g) was added under nitrogen. A solution of (1S,2S)-Ethyl 2-((S)-1-phenylethylamino)cyclohexanecarboxylate (10, 237.9 g) in tetrahydrofuran (0.35 L) was added and the reaction mixture was heated to reflux for NLT 12 hours, under nitrogen. The mixture was cooled to below 10° C. and acetic acid (NLT 278 mL) was added, while maintaining the temperature between 5-15° C. in NLT 30 minutes. 25% aqueous sodium hydroxide solution (1.78 L) and water (˜2 L) were added to adjust pH to ˜8.7. The aqueous layer was separated and extracted with 2×0.75 L of heptanes, which was kept aside. The organic layer was concentrated to about 0.8 L volume and combined with the heptane extracts and additional water (0.75 L). The aqueous layer was separated and extracted with heptanes (0.75 L) and the combined organic extracts were washed with water (2×0.75 L), 3.5 M aqueous sodium chloride solution (0.75 L) and dried using anhydrous magnesium sulfate. The filtered solution was concentrated under vacuum and provided 184.1 g) of (1S,2S)-2-[(S)-1-phenylethyl amino]cyclohexyl)methanol (11) as the major isomer.

Provenance & Evidence