Imidazole → HCID 178494315, compound

HRID 2095733Notes

Reaction equation

HRID 2095733 reaction equation
[I:1][C:2]1[C:3]([O:14][CH3:15])=[N:4][N:5]([C@H:7]2[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]2)[CH:6]=1.N1C=CN=C1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Si:21]([O:13][C@H:10]1[CH2:9][CH2:8][C@H:7]([N:5]2[CH:6]=[C:2]([I:1])[C:3]([O:14][CH3:15])=[N:4]2)[CH2:12][CH2:11]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 178494313HCID 178494313, compound

Product 1

HCID 178494315HCID 178494315, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of trans-4-(4-iodo-3-methoxy-1H-pyrazol-1-yl)cyclohexanol (0.359 g, 1.11 mmol), 1H-imidazole (0.228 g, 3.34 mmol), and 4-dimethylaminopyridine (0.0272 g, 0.223 mmol) in anhydrous DCM (10.8 mL) was charged with tert-butyldimethylsilyl chloride (0.336 g, 2.23 mmol) and stirred at rt for 20 min. The reaction was partitioned between CHCl3 and 1M NaHCO3 and separated. The aqueous was re-extracted with CHCl3 (3×) and the combined organic fraction were washed with brine (1×), dried over Na2SO4, filtered and concentrated in vacuo resulting in a crude colorless oil. The crude material was purified by chromatography on silica gel [eluting with 5% EtOAc in hexanes] resulting in the title compound as a clear colorless oil. 1H NMR (400 MHz, CD3OD): δ=0.09 (d, J=0.51 Hz, 6H), 0.91 (s, 9H), 1.41-1.54 (m, 2H), 1.74-1.87 (m, 2H), 1.93-2.09 (m, 4H), 3.68-3.77 (m, 1H), 3.86 (d, J=0.5 Hz, 3H), 3.96 (tt, J=3.9, 12 Hz, 1H), 7.48 (s, 1H). MS (ES+): m/z 437.17 (100) [MH+]. HPLC: tR=4.98 min (vvnonpolar—5 min, ZQ3).

Workup

  1. customThe reaction was partitioned between CHCl3 and 1M NaHCO3
  2. customseparated
  3. extractionThe aqueous was re-extracted with CHCl3 (3×)
  4. washthe combined organic fraction were washed with brine (1×)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customresulting in a crude colorless oil
  9. customThe crude material was purified by chromatography on silica gel [eluting with 5% EtOAc in hexanes]

Sources & evidence

ORD record
ord-b27113b185b343468324d654be7b44bc
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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