Hydrochloric Acid → {(2S,4R)-1-[4-methyl-1-(3-methylbutyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid

Participants

Reaction Conditions

Reaction Steps

A solution of LiOH (1.6 g, 67 mmol) in H2O (15 ml) was added to a stirred solution of methyl {(2S,4R)-1-[4-methyl-1-(3-methylbutyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Step 1, 6.0 g, 13.2 mmol) in THF (15 ml) at RT. The mixture was stirred and heated at 60° C. for 18 hrs. After cooling to RT 2N HCl (35 ml) was added and the THF was removed in vacuo. The residue was partitioned between CH2Cl2/H2O. The pH of the aqueous layer was adjusted to pH7 with saturated aqueous NaHCO3. The aqueous layer was extracted with CH2Cl2 (×3). The combined extracts were dried (Na2SO4) filtered and evaporated. The residue was purified by chromatography (silica, 4-8% MeOH/CH2Cl2) to give the acid (5.7 g) as a colourless solid. 1H NMR (500 MHz, CD3OD): δ 0.68-0.75 (1H, m), 0.83-0.87 (12H, m), 0.97-1.09 (2H, m), 1.10-1.17 (1H, m), 1.32-1.50 (7H, m), 1.69-1.75 (1H, m), 1.86-2.00 (3H, m), 2.16-2.24 (2H, m), 2.25-2.31 (1H, m), 2.54 (1H, t, J 11.6), 3.17 (1H, d, J 11.8), 3.93 (1H, d, J 10.3), 7.54 (2H, brd, J 7), 7.65 (2H, d, J 8.2); M/Z (ES+) 442 (MH+).

Provenance & Evidence