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

HRID 490209Notes

Reaction equation

HRID 490209 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.C([Li])CCC.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>O1CCCC1>[OH:25][C:22]1([C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:21][CH2:20][N:19]([C:17]([O:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:18])[CH2:24][CH2:23]1

Participants

5

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 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

1-Methylimidazole (4.1 mL, 50 mmol) in dry tetrahydrofuran was treated with n-butyllithium (25 mL, 50 mmol) at room temperature and heated at 40° C. for 3 hours. The reaction was cooled to −78° C. and 4-oxo-piperidine-1-carboxylic acid tert-butylester (9.96 g, 50 mmol) added. The mixture was allowed to warm to room temperature, stirred for 6 hours the heated to 40° C. for an additional 3 hours. The reaction was cooled to room temperature, quenched with water and extracted with ethyl acetate. The organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was recrystallized from methanol to provide the title compound (8.2 g, 84%) as white solid. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.8 (d, 2H, J=15 Hz), 2.1 (m, 2H), 3.3 (t, 3H, J=15 Hz), 3.8 (s, 4H), 6.8 (dd, 2H, J=9, 3 Hz); MS (DCI/NH3) m/e 282 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to −78° C.
  2. temperatureto warm to room temperature
  3. temperatureheated to 40° C. for an additional 3 hours
  4. temperatureThe reaction was cooled to room temperature
  5. customquenched with water
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic phases were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was recrystallized from methanol

Sources & evidence

ORD record
ord-3386d8336fb94cc4a4d354e8b02b9ab6
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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