Reaction Steps
To a solution of trans-4-hydroxycyclohexanecarboxylic acid (1.00 g, 6.94 mmol), 2,2-dimethoxy-N-methylethanamine (0.909 g, 7.63 mmol), and 1-Hydroxybenzotriazole hydrate (1.17 g, 7.63 mmol) in DMF (25 mL, 320 mmol) was added N-(3-Dimethylaminopropyl)-W-ethylcarbodiimide hydrochloride (1.46 g, 7.63 mmol) at ambient temperature, and the solution was stirred at ambient temperature overnight. Most of the DMF was evaporated in vacuo, and the residue was partitioned between water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc (4×25 mL), saturated with NaCl, and extracted again with EtOAc (5×25 mL). The combined EtOAc extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as yellow oil that was used without further purification in the next step. 1H NMR (400 MHz, CDCl3): δ=4.48 (t, J=5.4 Hz, 1H, major rotamer), 4.39 (t, J=5.4 Hz, 1H, minor rotamer), 3.70-3.61 (m, 1H), 3.45-3.42 (m, 2H), 3.43 (s, 6H, minor rotamer), 3.40 (s, 6H, major rotamer), 3.11 (s, 3H, major rotamer), 2.97 (s, 3H, minor rotamer), 2.56 (tt, J=11.6, 3.8 Hz, 1H, minor rotamer), 2.46 (tt, J=11.8, 3.4 Hz, 1H, major rotamer), 2.11-2.00 (m, 2H), 1.86-1.74 (m, 2H), 1.71-1.55 (m, 3H), 1.36-1.23 (m, 2H). MS (ES+): m/z=268.11 (87) [MNa+], 246.15 (42) [MH+], 214.13 (100) [MH+−MeOH]. HPLC: tR=2.36 min (polar—5 min, ZQ3).
