Potassium Phosphate, Tribasic → Ethyl 2,6-diethoxy-4'-fluorobiphenyl-4-carboxylate

HRID 531044Notes

Reaction equation

HRID 531044 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Br[C:39]1[C:49]([O:50][CH2:51][CH3:52])=[CH:48][C:42]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:41][C:40]=1[O:53][CH2:54][CH3:55]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:54]([O:53][C:40]1[CH:41]=[C:42]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH:48]=[C:49]([O:50][CH2:51][CH3:52])[C:39]=1[C:13]1[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=1)[CH3:55]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2856454-Fluorophenylboronic acidHCID 10663268Ethyl 4-bromo-3,5-diethoxybenzoate

Product 1

HCID 66644576Ethyl 2,6-diethoxy-4'-fluorobiphenyl-4-carboxylateYield 86.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Palladium acetate (1.98 g), tripotassium phosphate (112 g), (4-fluorophenyl)boronic acid (43.1 g), and tricyclohexylphosphine (20% toluene solution, 31.2 mL) were added to a mixture of ethyl 4-bromo-3,5-diethoxybenzoate (55.8 g) in toluene (300 mL) and water (150 mL), and the resultant mixture was heated with stirring overnight at 90° C. in an argon atmosphere. The reaction mixture was allowed to cool to room temperature, and then, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated saline in this order. The organic layer was dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (50.7 g).

Workup

  1. temperatureto cool to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water and saturated saline in this order
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-1882da3be62542f482d418f42ce0b1de
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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