Hydrochloric Acid → 3-[4-(2,2-dimethylpropyl)-1H-imidazol-2-yl]-1,1-difluoro-2-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]propan-2-ol

HRID 216365Notes

Reaction equation

HRID 216365 reaction equation
Cl.[CH3:2][C:3]([CH3:48])([CH3:47])[CH2:4][C:5]1[N:6]=[C:7]([CH2:29][C:30]([C:35]2[CH:40]=[CH:39][C:38]([C:41]3[N:45]([CH3:46])[N:44]=[CH:43][CH:42]=3)=[CH:37][CH:36]=2)([OH:34])[CH:31]([F:33])[F:32])[N:8](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:9]=1>CO>[CH3:2][C:3]([CH3:48])([CH3:47])[CH2:4][C:5]1[N:6]=[C:7]([CH2:29][C:30]([C:35]2[CH:40]=[CH:39][C:38]([C:41]3[N:45]([CH3:46])[N:44]=[CH:43][CH:42]=3)=[CH:37][CH:36]=2)([OH:34])[CH:31]([F:32])[F:33])[NH:8][CH:9]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 686681093-[4-(2,2-dimethylpropyl)-1-trityl-1H-imidazol-2-yl]-1,1-difluoro-2-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]propan-2-ol

Product 1

HCID 1784817853-[4-(2,2-dimethylpropyl)-1H-imidazol-2-yl]-1,1-difluoro-2-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]propan-2-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Hydrogen chloride (4 M in 1,4-dioxane) (1 mL, 0.25 mmol) was added to an ambient temperature solution of 3-[4-(2,2-dimethylpropyl)-1-trityl-1H-imidazol-2-yl]-1,1-difluoro-2-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]propan-2-ol (30 mg, 0.05 mmol) in methanol (1 mL). After stirring at 70° C. for 1 h, volatiles were removed in vacuo. The residue was partitioned between diethyl ether and 1 N hydrochloric acid. The aqueous phase was washed with diethyl ether, basified with 2.5 N aqueous sodium hydroxide and extracted with ethyl acetate. Combined extracts were washed with brine, dried (sodium sulfate) and concentrated in vacuo to afford the title compound. 1H NMR (500 MHz, CD3OD) δ 7.58 (d, J=8.0 Hz, 2H), 7.46 (d, J=1.5 Hz, 1H), 7.39 (d, J=8.0 Hz, 2H), 6.51 (s, 1H), 6.30 (d, J=1.5 Hz, 1H), 5.98 (t, J=55.7 Hz, 1H), 3.81 (s, 3H), 3.42-3.28 (m, 2H), 2.31 (s, 2H), 0.76 (s, 9H).

Workup

  1. customvolatiles were removed in vacuo
  2. customThe residue was partitioned between diethyl ether and 1 N hydrochloric acid
  3. washThe aqueous phase was washed with diethyl ether
  4. extractionextracted with ethyl acetate
  5. washCombined extracts were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4fa15cefcd784cfc8503421c48964d7e
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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