Hydrochloric Acid → HCID 66559225, compound

Participants

Reaction Steps

To a solution of 2-chloro-1-ethynyl-4-methoxybenzene (15 mg, 0.093 mmol, 1 eq) and (2R)-4-azido-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (30 mg 0.093 mmol, 1 eq) in EtOH—H2O (7 mL:1 mL) was added sodium ascorbate (19 mg, 0.093 mmol, 1 eq) and CuSO4 (9 mg, 0.037 mmol, 0.4 eq). The reaction mixture was stirred vigorously at RT overnight. The reaction mixture was concentrated to remove the EtOH/H2O. The residue was dissolved in EtOAc and the CuSO4 solid was filtered off. The filtrated was adsorbed onto silica and purified by flash chromatography on a 12 g silica gel column eluting with 0-100% EtOAc/Hpt to give (2R)-4-[4-(2-chloro-4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (18 mg). To a solution of (2R)-4-[4-(2-chloro-4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (18 mg, 0.037 mmol, 1 eq) in EtOH (93 mL) was added 4 M HCl. The reaction mixture was allowed to stir at RT for 3 h and then concentrated to give (2R)-4-[4-(2-chloro-4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide (10 mg, 67% yield). 1H NMR (400 MHz, METHANOL-d4) δ 8.69 (s, 1H), 7.80 (d, J=8.6 Hz, 1H), 7.15 (d, J=2.5 Hz, 1H), 7.09-7.02 (m, 1H), 4.85-4.73 (m, 1H), 4.71-4.57 (m, 1H), 3.87 (s, 3H), 3.07 (s, 4H), 2.63-2.50 (m, 1H), 1.69 (s, 3H). LC-MS M+H+403.1.

Provenance & Evidence