1-Methylimidazole → tert-butyl 4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 1910390Notes

Reaction equation

HRID 1910390 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.C([Li])CCC.[O:12]=[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1>C1COCC1.CCCCCC>[OH:12][C:13]1([C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 13901-MethylimidazoleHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 68570244tert-butyl 4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)piperidine-1-carboxylateYield 58.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 1-methyl-1H-imidazole (2 g) in THF (15 ml) was added 1.59 M n-butyllithium in n-hexane solution (18.4 ml) slowly under ice bath cooling, and the mixture was stirred at room temperature for 3 hours. To this reaction mixture was added tert-butyl 4-oxopiperidine-1-carboxylate (5.8 g) in THF (15 ml) solution and the mixture was stirred at room temperature for 2 hours. The reaction mixture was extracted with EtOAc and was washed with brine, and was dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by silica gel column (CHCl3:MeOH=95:5 to 90:10) to give tert-butyl 4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)piperidine-1-carboxylate (4.02 g) as a pale yellow powder.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. extractionThe reaction mixture was extracted with EtOAc
  4. washwas washed with brine
  5. dry with materialwas dried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe residue was purified by silica gel column (CHCl3:MeOH=95:5 to 90:10)

Sources & evidence

ORD record
ord-bc019edbe64a4ef1844c856ccf157632
Source dataset
uspto-grants-2013_12
Patent number
US08603975B2

Reaction notes

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