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

HRID 928785Notes

Reaction equation

HRID 928785 reaction equation
[OH:1][CH:2]([C:16]1[N:20]([CH3:21])[CH:19]=[N:18][CH:17]=1)[CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1>O1CCOCC1.O=[Mn]=O>[CH3:21][N:20]1[C:16]([C:2]([CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)=[O:1])=[CH:17][N:18]=[CH:19]1

Participants

4

Reactant 1

HCID 86715620tert-Butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate

Product 1

HCID 66677755tert-Butyl 4-(1-methyl-1H-imidazole-5-carbonyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalyst3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A homogeneous solution of tert-butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate (32.2 g, 109 mmol; Intermediate 42, 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 and additional MnO2 was added (48.0 g, 552 mmol) and the reaction stirred under 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 was flash chromatographed with an EtOAc to 50% acetone/EtOAc gradient to provide the title compound as a clear dark yellow oil.

Workup

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

Sources & evidence

ORD record
ord-f8085834ad274ad6b8ebe7365d279a44
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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