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

Temperature

100 °C

A homogeneous solution of tert-butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate (32.2 g, 109 mmol; Intermediate 58: step a) in dioxane (436 mL) was treated with MnO2 (47.6 g, 547 mmol) and stirred at 100° C. under air overnight (17 hours). Since the reaction was only ˜50% complete by NMR, the reaction was cooled to room temperature, additional MnO2 (48.0 g, 552 mmol) was added and the reaction stirred under air at 100° C. for 6.5 hours, then at room temperature for 18 days. The mixture was 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. The crude material was flash chromatographed with an EtOAc to 50% acetone/EtOAc gradient to provide the title compound as a clear dark yellow oil.

1. temperaturethe reaction was cooled to room temperature
2. stirringthe reaction stirred under air at 100° C. for 6.5 hours
3. waitat room temperature for 18 days
4. filtrationThe mixture was then filtered through a pad of Celite®
5. washthe black filter cake washed with EtOAc
6. stirringstirred at room temperature overnight
7. filtrationThe reaction was then filtered as above and
8. concentrationconcentrated
9. customto provide the crude title compound as a clear dark yellow oil
10. customchromatographed with an EtOAc to 50% acetone/EtOAc gradient

ORD record

ord-d06270186d71422990a0341127e93a94

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09284308B2