Sodium Carbonate → 4'-Methyl-4-biphenylcarboxylic acid

HRID 1785758Notes

Reaction equation

HRID 1785758 reaction equation
Br[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][CH:3]=1.[CH3:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>COCCOC.C(O)C.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>[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:3]=[CH:4][C:5]([C:6]([OH:8])=[O:7])=[CH:11][CH:12]=2)=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 22043Ethyl 4-bromobenzoateHCID 79799Tolylboronic acid

Product 1

HCID 20634214'-Methyl-4-biphenylcarboxylic acid

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A room temperature solution of ethyl 4-bromobenzoate (0.70 mL, 4.3 mmol) in DME (20 mL) was treated with Pd(PPh3)4 (246 mg, 0.2 mmol), stirred for 5 minutes, treated with a solution of 4-methylphenylboronic acid (870 mg, 6.4 mmol) in ethanol (10 mL), stirred for 5 minutes, treated with 2M Na2CO3 (18.0 mL, 36.0 mmol), heated to reflux, stirred for 16 hours, and concentrated. The concentrate was dissolved in water (75 mL) and diethyl ether (50 mL), filtered through celite, and extracted with diethyl ether. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 33% acetone/hexanes. The resulting product was dissolved in methanol (10 mL) and THY (5 mL), treated with 1M NaOH (4.3 mL, 4.3 mmol), stirred for 48 hours, concentrated, dissolved in water (10 mL), adjusted to pH 1 with 12M HCl, and filtered. Recrystallization from ethyl acetate provided the desired product. MS (APCI(+)) m/e 213 (M+H)+.

Workup

  1. stirringstirred for 5 minutes
  2. temperatureheated
  3. temperatureto reflux
  4. stirringstirred for 16 hours
  5. concentrationconcentrated
  6. dissolutionThe concentrate was dissolved in water (75 mL)
  7. filtrationdiethyl ether (50 mL), filtered through celite
  8. extractionextracted with diethyl ether
  9. washThe combined extracts were washed with brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe concentrate was purified by flash column chromatography on silica gel with 33% acetone/hexanes
  14. dissolutionThe resulting product was dissolved in methanol (10 mL)
  15. stirringstirred for 48 hours
  16. concentrationconcentrated
  17. dissolutiondissolved in water (10 mL)
  18. filtrationfiltered
  19. customRecrystallization from ethyl acetate

Sources & evidence

ORD record
ord-0f352fa8ef93451092bd923eb2108a51
Source dataset
uspto-grants-2009_03
Patent number
US07504512B2

Reaction notes

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