Hydrochloric Acid → ethyl (3-{3-[5-(2',6'-dimethylbiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate

HRID 2389332Notes

Reaction equation

HRID 2389332 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11](=[O:30])[N:12]([CH2:14][CH2:15][CH2:16][C:17]2[CH:18]=[C:19]([CH:27]=[CH:28][CH:29]=2)[O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:13]=1.[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11](=[O:30])[N:12]([CH2:14][CH2:15][CH2:16][C:17]2[CH:18]=[C:19]([CH:27]=[CH:28][CH:29]=2)[O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:13]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 5833222,6-Dimethylphenylboronic acid2×HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl2×HCID 86637905ethyl (3-{3-[5-(2-bromophenyl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate

Product 1

HCID 86637906ethyl (3-{3-[5-(2',6'-dimethylbiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetateYield 20.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl (3-{3-[5-(2-bromophenyl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate (255 mg), (2,6-dimethylphenyl)boronic acid (122 mg), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (26 mg), tripotassium phosphate (345 mg) and palladium (II) acetate (4 mg) in toluene (10 mL) was stirred under N2 gas atmosphere at 100° C. for 40 hours and cooled to ambient temperature. To the mixture was added 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (26 mg), (2,6-dimethylphenyl)boronic acid (50 mg) and palladium (II) acetate (4 mg) and the mixture was stirred under N2 gas atmosphere at 100° C. for 60 hours and cooled to ambient temperature. The reaction mixture was acidified with 1M HCl aqueous solution and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was dissolved in EtOH (10 mL). To the solution was added concentrated H2SO4(1.5 mL) and the mixture was refluxed for 1.5 hours and cooled to ambient temperature. The reaction mixture was neutralized with saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography (n-hexane:EtOAc=70:30) to give ethyl (3-{3-[5-(2′,6′-dimethylbiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate (55.1 mg) as a colorless oil.

Workup

  1. temperaturecooled to ambient temperature
  2. stirringthe mixture was stirred under N2 gas atmosphere at 100° C. for 60 hours
  3. temperaturecooled to ambient temperature
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. dissolutionThe residue was dissolved in EtOH (10 mL)
  10. additionTo the solution was added concentrated H2SO4(1.5 mL)
  11. temperaturethe mixture was refluxed for 1.5 hours
  12. temperaturecooled to ambient temperature
  13. extractionextracted with EtOAc
  14. washThe organic layer was washed with brine
  15. dry with materialdried over anhydrous MgSO4
  16. filtrationfiltered
  17. customevaporated in vacuo
  18. customThe residue was purified by silica gel column chromatography (n-hexane:EtOAc=70:30)

Sources & evidence

ORD record
ord-4315d5ba261d493bb88ae8e6cfd14cdf
Source dataset
uspto-grants-2012_09
Patent number
US08273745B2

Reaction notes

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