Sodium Carbonate → ethyl (3-{3-[5-(2'-methoxybiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate

HRID 2389331Notes

Reaction equation

HRID 2389331 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][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:31][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=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

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 86637905ethyl (3-{3-[5-(2-bromophenyl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate

Product 1

HCID 86637904ethyl (3-{3-[5-(2'-methoxybiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetateYield 30.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
98 °C

Procedure

A mixture of ethyl (3-{3-[5-(2-bromophenyl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate (235 mg), (2-methoxyphenyl)boronic acid (114 mg), Na2CO3(159 mg), Pd(PPh3)4 (29 mg) in toluene (8 mL) and water (4 mL) was stirred under N2 gas atmosphere at 98° C. for 30 hours and cooled to ambient temperature. The reaction mixture was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The aqueous layer of the reaction mixture was acidified with 1M HCl aqueous solution and extracted with EtOAc and the organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The filtrate and the residue of the first extract was combined and evaporated in vacuo. The residue was dissolved in EtOH (20 mL). To the solution was added concentrated H2SO4 (1.5 mL) at ambient temperature and refluxed for 1 hour. The reaction mixture was cooled to ambient temperature, neutralized with saturated NaHCO3 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 purified by silica gel column chromatography (n-hexane:EtOAc=60:40) to afford ethyl (3-{3-[5-(2′-methoxybiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate (75 mg) as a colorless oil.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionThe reaction mixture was extracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. extractionextracted with EtOAc
  8. washthe organic layer was washed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. extractionThe filtrate and the residue of the first extract
  13. customevaporated in vacuo
  14. dissolutionThe residue was dissolved in EtOH (20 mL)
  15. additionTo the solution was added concentrated H2SO4 (1.5 mL) at ambient temperature
  16. temperaturerefluxed for 1 hour
  17. temperatureThe reaction mixture was cooled to ambient temperature
  18. extractionextracted with EtOAc
  19. washThe organic layer was washed with brine
  20. dry with materialdried over anhydrous MgSO4
  21. filtrationfiltered
  22. customevaporated in vacuo
  23. customThe residue was purified by silica gel column chromatography (n-hexane:EtOAc=60:40)

Sources & evidence

ORD record
ord-7dee7b1d4d0e4eb9a484957382f9e47b
Source dataset
uspto-grants-2012_09
Patent number
US08273745B2

Reaction notes

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