C(OC(=O)[NH:10][C@@H:11]([CH:16]([CH3:18])[CH3:17])C(C#N)O)C1C=CC=CC=1.Cl.C1([O:27]C)C=CC=CC=1.[O:29]1[CH2:34][CH2:33][O:32]CC1>>[NH2:10][CH:11]([CH:16]([CH3:18])[CH3:17])[C@H:33]([OH:32])[C:34]([OH:29])=[O:27]To a solution of ((S)-2-Cyano-2-hydroxy-1-isopropyl-ethyl)-carbamic acid benzyl ester (10) (5.1 g, 19.5 mmol) in 1,4-dioxane (90 mL) was added conc. HCl (90 mL) and anisole (1.5 equiv.) and the mixture was heated to 110° C. for 18 h. The reaction mixture was cooled to ambient temperature and concentrated under vacuum to remove the dioxane. The mixture was then washed with EtOAc and the residue further concentrated under vacuum at 40° C. to remove the conc HCl. Any residual water was removed by azeotroping with toluene. The residue was washed with Et2O (2×50 mL) to afford hydroxyl acid (11) as a gummy solid (crude, mixture of diastereoisomers). 1H NMR (400 MHz, DMSO-d6): δ 8.20 (1H, brs), 7.96 (1H, brs), 4.42 (1H, d J=3.0 Hz), 4.17 (1H, d J=4.0 Hz), 3.17-3.05 (2H, m), 1.98-1.86 (2H, m), 0.96-0.86 (6H, m); m/z 148 (MH)+.
Loading…
