tert-Butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate → tert-Butyl 4-(1-methyl-1H-imidazole-5-carbonyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A homogeneous solution of tert-butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate (32.2 g, 109 mmol, Intermediate 1: step a) in 1,4-dioxane (436 mL) was treated with MnO2 (47.6 g, 547 mmol) and stirred at 100° C. open to the air overnight (17 hours). Since the reaction was only ˜50% complete by NMR, the reaction was cooled to room temperature and additional MnO2 was added (48.0 g, 552 mmol) and the reaction stirred open to the air at 100° C. for 6.5 hours, then at room temperature for 18 days, then filtered through a pad of Celite® and the black filter cake washed with EtOAc. The crude filtrate was treated with a third portion of MnO2 (28.5 g, 327 mmol) and stirred at room temperature overnight. The reaction was then filtered as above and concentrated to provide the crude title compound as a clear dark yellow oil. This oil was purified by FCC with an EtOAc to 50% acetone/EtOAc gradient to provide the title compound as a clear dark yellow oil.

Provenance & Evidence