Sodium hydride → (2R)-1-(3-Fluorobiphenyl-4-yloxy)-4-(3-pyridyl)-2-butanol

HRID 1600985Notes

Reaction equation

HRID 1600985 reaction equation
C1(C)C=CC(S([O:10][CH2:11][C@H:12]([O:21][Si](C(C)(C)C)(C)C)[CH2:13][CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)(=O)=O)=CC=1.[H-].[Na+].[F:32][C:33]1[CH:34]=[C:35]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:36]=[CH:37][C:38]=1O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C)C=O.O1CCCC1.[Cl-].[Na+].O>[F:32][C:33]1[CH:34]=[C:35]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:36]=[CH:37][C:38]=1[O:10][CH2:11][C@H:12]([OH:21])[CH2:13][CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 2724141Tetrabutylammonium FluorideHCID 130044482-Fluoro-4-phenylphenolHCID 54162583(2R)-2-(tert-butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate

Product 1

HCID 53961819(2R)-1-(3-Fluorobiphenyl-4-yloxy)-4-(3-pyridyl)-2-butanolYield 32.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Prepared according to the method described in Example 26e) from (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate (1.0 g), sodium hydride (60% dispersion in mineral oil, 0.115 g) and 3-fluorobiphenyl-4-ol (0.52 g) in dimethylformamide (15 ml). The adduct was dissolved in tetrahydrofuran (10 ml) and tetrabutylammonium fluoride (1.08 g) was added. The reaction was stirred at ambient temperature for 3 hours and was then poured into brine and extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was purified by column chromatography over silica eluting with dichloromethane:ethanol (19:1) to give the title compound as a white solid (0.25 g).

Workup

  1. customPrepared
  2. extractionextracted with ether
  3. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue obtained
  7. customwas purified by column chromatography over silica eluting with dichloromethane:ethanol (19:1)

Sources & evidence

ORD record
ord-2b56b1cbd8aa4f779e5b14d1cbbb1377
Source dataset
uspto-grants-1999_11
Patent number
US05977105

Reaction notes

Loading…