Potassium Phosphate, Tribasic → Ethyl 2-ethoxy-4'-fluoro-6-hydroxybiphenyl-4-carboxylate

HRID 530975Notes

Reaction equation

HRID 530975 reaction equation
Br[C:2]1[C:12]([OH:13])=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[O:14][CH2:15][CH3:16].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH2:15]([O:14][C:3]1[CH:4]=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:11]=[C:12]([OH:13])[C:2]=1[C:29]1[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=1)[CH3:16]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2856454-Fluorophenylboronic acidHCID 90423209Ethyl 4-bromo-3-ethoxy-5-hydroxybenzoate

Product 1

HCID 90423930Ethyl 2-ethoxy-4'-fluoro-6-hydroxybiphenyl-4-carboxylateYield 100%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Palladium acetate (344 mg) was added to a mixture of ethyl 4-bromo-3-ethoxy-5-hydroxybenzoate (8.87 g), tripotassium phosphate (19.5 g), (4-fluorophenyl)boronic acid (10.7 g), tricyclohexylphosphine (20% toluene solution, 5.45 mL), toluene (80 mL), and water (40 mL), and the resultant mixture was stirred overnight at 90° C. in an argon atmosphere. The reaction mixture was allowed to cool to room temperature, then diluted with ethyl acetate, and 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 (9.34 g).

Workup

  1. washwashed with water and saturated saline in this order
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d00790692f3f4d2ba4859883c5c104a1
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

Loading…