Hydrochloric Acid → 4-(4-amino-phenyl)-4',6'-dimethyl-3,4,5,6-tetrahydro-2H-[1,2']-bipyridinyl-4-ol

HRID 37871Notes

Reaction equation

HRID 37871 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([N:13]([Si](C)(C)C)[Si](C)(C)C)=[CH:9][CH:8]=1.[CH3:22][C:23]1[CH:28]=[C:27]([CH3:29])[N:26]=[C:25]([N:30]2[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]2)[CH:24]=1.Cl.[OH-].[Na+]>C(OCC)C.O1CCCC1>[NH2:13][C:10]1[CH:11]=[CH:12][C:7]([C:33]2([OH:36])[CH2:32][CH2:31][N:30]([C:25]3[CH:24]=[C:23]([CH3:22])[CH:28]=[C:27]([CH3:29])[N:26]=3)[CH2:35][CH2:34]2)=[CH:8][CH:9]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 40926204-Bromo-N,N-bis(trimethylsilyl)anilineHCID 668513404',6'-Dimethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-oneHCID 178418339Butyllithium

Product 1

HCID 668511514-(4-amino-phenyl)-4',6'-dimethyl-3,4,5,6-tetrahydro-2H-[1,2']-bipyridinyl-4-olYield 57.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

n-Butyl lithium (1 mL, 1.6 M in hexane, 1.6 mmol) was added dropwise to a solution of 2-(4-bromo-phenyl)-1,1,1,3,3,3-hexamethyl-disilazane (0.7 g, 2.20 mmol) in dry diethyl ether (10 mL) and stirred at room temperature for 15 min then cooled in an ice bath. A solution of 4′,6′-dimethyl-2,3,5,6-tetrahydro-[1,2′]bipyridinyl-4-one (0.3 g, 1.47 mmol) in dry tetrahydrofuran (15 mL) was added and the resulting mixture heated at 50° C. for 2.5 h. The reaction mixture was brought to room temperature and stirred overnight, then cooled to 0° C. and quenched into ammonium chloride solution. The mixture was extracted with ethyl acetate and the organic phase was washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to yield the crude compound, to which was added 2N HCl and the resulting mixture was stirred overnight at room temperature. The pH of the solution was adjusted to pH 10 with dilute sodium hydroxide then the mixture was extracted with chloroform. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give a viscous red oil which was purified by washing with pentane (5×10 mL) to afford 4-(4-amino-phenyl)-4′,6′-dimethyl-3,4,5,6-tetrahydro-2H-[1,2′]-bipyridinyl-4-ol (0.25 g, 57%).

Workup

  1. temperaturethen cooled in an ice bath
  2. temperaturethe resulting mixture heated at 50° C. for 2.5 h
  3. customwas brought to room temperature
  4. stirringstirred overnight
  5. temperaturecooled to 0° C.
  6. customquenched into ammonium chloride solution
  7. extractionThe mixture was extracted with ethyl acetate
  8. washthe organic phase was washed with water, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto yield the crude compound
  13. stirringthe resulting mixture was stirred overnight at room temperature
  14. extractionthe mixture was extracted with chloroform
  15. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated to dryness
  18. customto give a viscous red oil which
  19. customwas purified
  20. washby washing with pentane (5×10 mL)

Sources & evidence

ORD record
ord-793a2a880071469eb439c4a4b98eddc5
Source dataset
uspto-grants-2013_09
Patent number
US08524705B2

Reaction notes

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