Methanol → 2-methyl-1-[1-(tetrahydro-pyran-2-yl)-1H-imidazol-2-yl]-propan-2-ol

HRID 2044509Notes

Reaction equation

HRID 2044509 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.[Li]CCCC.[CH3:17][C:18]1([CH3:21])[CH2:20][O:19]1.CO>C1COCC1>[CH3:17][C:18]([OH:19])([CH3:21])[CH2:20][C:8]1[N:7]([CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH:11]=[CH:10][N:9]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 11208Isobutylene oxideHCID 587436211-(Tetrahydro-2H-pyran-2-yl)-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 582043162-methyl-1-[1-(tetrahydro-pyran-2-yl)-1H-imidazol-2-yl]-propan-2-olYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of 1-(tetrahydro-pyran-2-yl)-1H-imidazole (7.6 g, 50 mmol) in dry THF (500 ml) at −78° C. was added n-BuLi solution (2.5 M in hexanes, 25 mL, 60 mmol, 1.2 equiv). The reaction mixture was slowly warmed to 0° C. and stirred at 0° C. for 30 min. After it was cooled to −78° C., 2,2-dimethyloxirane (7.2 g, 100 mmol) was added and it was stirred for 1 h. The reaction mixture was warmed to r.t. slowly and stirred at r.t. overnight. MeOH was added and the reaction mixture was concentrated by a rotary evaporator. Water (30 ml) was added and it was extracted with CH2Cl2 (15 ml×3). The organic layer was dried over MgSO4, concentrated, and purified by neutral Al2O3 column chromatography (CH2Cl2: MeOH=100:1) to give 8 gm of 2-methyl-1-[1-(tetrahydro-pyran-2-yl)-1H-imidazol-2-yl]-propan-2-ol (75%). 1H NMR (CDCl3): δ 7.04 (s, 1H), 6.95 (s, 1H), 5.13 (dd, J=2.6, 9.5 Hz, 1H), 4.05-4.02 (m, 1H), 3.68-3.62 (m, 1H), 2.82 (d, J=12.0 Hz, 2H), 2.01-1.89 (m, 4H), 1.92 (m, 1H), 1.69-1.60 (m, 3H), 1.24 (m, 6H)

Workup

  1. temperatureAfter it was cooled to −78° C.
  2. stirringit was stirred for 1 h
  3. temperatureThe reaction mixture was warmed to r.t. slowly
  4. stirringstirred at r.t. overnight
  5. concentrationthe reaction mixture was concentrated by a rotary evaporator
  6. additionWater (30 ml) was added
  7. extractionit was extracted with CH2Cl2 (15 ml×3)
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationconcentrated
  10. custompurified by neutral Al2O3 column chromatography (CH2Cl2: MeOH=100:1)

Sources & evidence

ORD record
ord-1ce253f1f12d418b8bdc3ddd63be4a23
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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