Imidazole → 4-{[tert-Butyl(dimethyl)silyl]oxy}-1-(1-methyl-1H-imidazol-2-yl)piperidine

HRID 2095744Notes

Reaction equation

HRID 2095744 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[N:7]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].N1C=CN=C1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Si:14]([O:13][CH:10]1[CH2:9][CH2:8][N:7]([C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:12][CH2:11]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 621338431-(1-Methyl-1H-imidazol-2-yl)piperidin-4-ol

Product 1

HCID 670039784-{[tert-Butyl(dimethyl)silyl]oxy}-1-(1-methyl-1H-imidazol-2-yl)piperidine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 1-(1-Methyl-1H-imidazol-2-yl)piperidin-4-ol (0.200 g, 1.10 mmol), tert-Butyldimethylsilyl chloride (0.333 g, 2.21 mmol), 4-Dimethylaminopyridine (30 mg, 0.2 mmol), 1H-Imidazole (225 mg, 3.31 mmol) and DCM (6.0 mL, 94 mmol) was stirred at ambient temperature for 1 h. The reaction mixture was diluted with DCM to ≈60 mL, washed with sat. NaHCO3 solution, water, and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel [Isco Combiflash, 2.5 g loading column/12 g column, eluting with DCM→5% MeOH in DCM]. Fractions containing the title compound were combined and dried in vacuo overnight, giving the title compound as yellow oil. 1H NMR (400 MHz, CDCl3): δ=6.77 (d, J=1.2 Hz, 1H), 6.65 (d, J=1.4 Hz, 1H), 3.85 (tt, J=8.0, 3.8 Hz, 1H), 3.47 (s, 3H), 3.28-3.21 (m, 2H), 2.91 (br ddd, J=12.0, 9.0, 3.0 Hz, 2H), 1.92-1.84 (m, 2H), 1.73-1.64 (m, 2H), 0.90 (s, 9H), 0.07 (s, 6H). MS (ES+): m/z=296.29 (100) [MH+]. HPLC: tR=3.22 min (verypolar—5 min, ZQ3). UV: λmax≈240 nm.

Workup

  1. washwashed with sat. NaHCO3 solution, water, and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed on silica gel [Isco Combiflash, 2.5 g loading column/12 g column, eluting with DCM→5% MeOH in DCM]
  6. additionFractions containing the title compound
  7. customdried in vacuo overnight

Sources & evidence

ORD record
ord-4a1daee541db46e8b656d3b531b2c4cc
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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