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

HRID 1910815Notes

Reaction equation

HRID 1910815 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 57.3%

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 organics were extracted with ethyl acetate, washed with water, brine, dried over anhydrous sodium sulfate, filtered and evaporated 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 and the organics extracted with chloroform. The extract was dried over anhydrous sodium sulfate, filtered and evaporated to dryness to give a red viscous 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, 57.3%).

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 organics were extracted with ethyl acetate
  8. washwashed with water, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customto yield the crude compound
  13. stirringthe resulting mixture was stirred overnight at room temperature
  14. extractionthe organics extracted with chloroform
  15. dry with materialThe extract was dried over anhydrous sodium sulfate
  16. filtrationfiltered
  17. customevaporated to dryness
  18. customto give a red viscous oil which
  19. customwas purified
  20. washby washing with pentane (5×10 mL)

Sources & evidence

ORD record
ord-3a90967624d945c78a7a5d324a6b1ee2
Source dataset
uspto-grants-2013_12
Patent number
US08604029B2

Reaction notes

Loading…