Cesium fluoride → HCID 68668109, compound

HRID 216364

Reaction equation

HRID 216364 reaction equation
[CH3:1][N:2]1[C:6]([Sn](CCCC)(CCCC)CCCC)=[CH:5][CH:4]=[N:3]1.Br[C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:61])([CH2:31][C:32]2[N:33]([C:42]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH:34]=[C:35]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[N:36]=2)[CH:28]([F:30])[F:29])=[CH:23][CH:22]=1.[F-].[Cs+]>O1CCCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:39][C:38]([CH3:41])([CH3:40])[CH2:37][C:35]1[N:36]=[C:32]([CH2:31][C:27]([C:24]2[CH:25]=[CH:26][C:21]([C:6]3[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=3)=[CH:22][CH:23]=2)([OH:61])[CH:28]([F:29])[F:30])[N:33]([C:42]([C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:34]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 218674551-Methyl-5-(tributylstannyl)-1H-pyrazoleHCID 686683682-(4-bromophenyl)-3-[4-(2,2-dimethylpropyl)-1-trityl-1H-imidazol-2-yl]-1,1-difluoropropan-2-ol

Product 1

HCID 68668109HCID 68668109, compound

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

Bis(triphenylphosphine) palladium (II) chloride (49 mg, 0.07 mmol) was added to a degassed, ambient temperature solution of 1-methyl-5-(tributylstannyl)-1H-pyrazole (259 mg, 0.70 mmol) and 2-(4-bromophenyl)-3-[4-(2,2-dimethylpropyl)-1-trityl-1H-imidazol-2-yl]-1,1-difluoropropan-2-ol (483 mg, 0.77 mmol) in tetrahydrofuran (15 mL). After stirring at 75° C. overnight, the reaction mixture was cooled and cesium fluoride (50% on celite) was added. After stirring vigorously at ambient temperature for 1 h, the reaction mixture was filtered, rinsing with ethyl acetate. The filtrate was washed with water, dried (magnesium sulfate), filtered and concentrated in vacuo. Chromatography over silica eluting with 0-100% ethyl acetate/hexane afforded 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.

Workup

  1. temperaturethe reaction mixture was cooled
  2. stirringAfter stirring vigorously at ambient temperature for 1 h
  3. filtrationthe reaction mixture was filtered
  4. washrinsing with ethyl acetate
  5. washThe filtrate was washed with water
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-67a203e52ab0405785e6459910bc177b
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Linked notes

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