p-Toluenesulfonic acid → 1-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-iodo-1H-pyrazole

HRID 2279838Notes

Reaction equation

HRID 2279838 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[I:12][C:13]1[CH:14]=[N:15][N:16]([CH2:18][C:19]([CH3:23])([CH3:22])[CH2:20][OH:21])[CH:17]=1.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>C(Cl)Cl.CCOC(C)=O>[CH3:22][C:19]([CH3:23])([CH2:20][O:21][CH:25]1[CH2:26][CH2:27][CH2:28][CH2:29][O:24]1)[CH2:18][N:16]1[CH:17]=[C:13]([I:12])[CH:14]=[N:15]1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 678114803-(4-Iodopyrazol-1-yl)-2,2-dimethylpropan-1-ol2×

Product 1

HCID 866977771-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-iodo-1H-pyrazoleYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

p-Toluenesulfonic acid (44 mg, 0.26 mmol) was added to a stirring solution of 3-(4-iodopyrazol-1-yl)-2,2-dimethyl-propan-1-ol (Compound 47E, 500 mg, 1.79 mmol) in DCM (2.58 mL). The mixture was stirred under argon, chilled in an ice-bath, then dihydropyran (0.261 mL, 2.86 mmol) was added, stirred and gradually warmed to rt over 16 hrs. The reaction mixture was diluted with EtOAc and washed with brine (2×), dried over sodium sulfate, filtered and concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0→10% EtOAc/Heptanes] to afford 597 mg of the title compound (92%). 1H NMR (400 MHz, CD3OD) δ 7.71 (s, 1H), 7.48 (s, 1H), 4.57 (t, J=3.5 Hz, 1H), 4.04-4.12 (m, 2H), 3.86 (d, J=3.0 Hz, 1H), 3.48-3.56 (m, 1H), 3.45 (d, J=9.3 Hz, 1H), 3.03 (d, J=9.6 Hz, 1H), 1.81-1.91 (m, 1H), 1.67-1.78 (m, 1H), 1.51-1.66 (m, 4H), 0.93 (d, J=4.8 Hz, 6H).

Workup

  1. temperaturechilled in an ice-bath
  2. stirringstirred
  3. washwashed with brine (2×)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified

Sources & evidence

ORD record
ord-bb3a387cd26c41db96616265df3e1072
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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