Sodium Carbonate → Methyl 2'-chloro-1,1'-biphenyl-4-carboxylate

HRID 915627Notes

Reaction equation

HRID 915627 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O.O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[Cl:12])=[CH:6][CH:5]=1)=[O:11]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 12081Methyl 4-bromobenzoateHCID 27343222-Chlorophenylboronic acid

Product 1

HCID 1393555Methyl 2'-chloro-1,1'-biphenyl-4-carboxylate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Combine methyl-4-bromobenzoate (1.0 g, 4.65 mmol), 2-chlorophenylboronic acid (799 mg, 5.1 mmol), Pd(OAc)2 (51 mg, 0.46 mmol) and sodium carbonate (1.5 g, 13.9 mmol) in dimethylformamide (20 mL) and water (2.0 mL) with stirring. Purge the reaction mixture with argon, add triphenylphosphine (61 mg, 0.23 mmol) and purge again with argon. Place the sealed reaction in an oil bath maintained at 80° C. and allow to stir for 1 hour. Cool the reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over magnesium sulfate, filter and evaporate. Purification by flash column chromatography yields 2′-chlorobiphenyl-4-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in tetrahydrofuran (0.25M) and add an equal volume of 1M sodium hydroxide. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCl and extract with ethyl acetate. Evaporation of the solvent yields 762 mg (67%) of the title compound. MS (m/e): 231.1 (M−).

Workup

  1. customPurge the reaction mixture with argon
  2. custompurge again with argon
  3. customthe sealed reaction in an oil bath
  4. temperatureCool
  5. customthe reaction to room temperature
  6. filtrationfilter through a short plug of celite with additional ethyl acetate
  7. washWash the organics with water
  8. dry with materialdry over magnesium sulfate
  9. filtrationfilter
  10. customevaporate
  11. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-d67fca9ffc5d42a8a2df55e1ba9fddd1
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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