1-Bromo-2-naphthol → 1-(3-Chloro-2-fluorophenyl)-2-naphthol

HRID 2205067Notes

Reaction equation

HRID 2205067 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[OH:12].[Cl:13][C:14]1[C:15]([F:23])=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)C.C1(C)C=CC=CC=1>[Cl:13][C:14]1[C:15]([F:23])=[C:16]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[CH:4][C:3]=2[OH:12])[CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 113161-Bromo-2-naphtholHCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 162171583-Chloro-2-fluorophenylboronic Acid

Product 1

HCID 867176881-(3-Chloro-2-fluorophenyl)-2-naphtholYield 44%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

In a 200-mL three-neck flask were put 5.8 g (26 mmol) of 1-bromo-2-naphthol, 4.5 g (26 mmol) of 3-chloro-2-fluorobenzeneboronic acid, and 0.40 g (1.3 mmol) of tri(ortho-tolyl)phosphine, and the air in the flask was replaced with nitrogen. To this mixture, 150 mL of toluene, 50 mL of ethanol, and 21 mL of an aqueous solution of potassium carbonate (2.0 mol/L) were added. The mixture was degassed by being stirred while the pressure in the flask was reduced; then, the air in the flask was replaced with nitrogen. To this mixture was added 58 mg (0.26 mmol) of palladium(II)acetate, and the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours. After stirring, the organic layer of the mixture was washed with water and the aqueous layer was subjected to extraction with toluene. The solution of the extract combined with the organic layer was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over magnesium sulfate. The resulting mixture was gravity-filtered, and the resulting filtrate was concentrated to give a brown liquid. The liquid was purified by silica gel column chromatography using a mixed solvent (toluene: hexane=9:1) as a developing solvent, so that 3.1 g of a brown liquid of a target substance was produced in a yield of 44%.

Workup

  1. customIn a 200-mL three-neck flask were put
  2. customThe mixture was degassed
  3. stirringthe resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours
  4. stirringAfter stirring
  5. washthe organic layer of the mixture was washed with water
  6. extractionthe aqueous layer was subjected to extraction with toluene
  7. washwas washed with a saturated aqueous solution of sodium chloride
  8. dry with materialthe organic layer was dried over magnesium sulfate
  9. filtrationThe resulting mixture was gravity-filtered
  10. concentrationthe resulting filtrate was concentrated
  11. customto give a brown liquid
  12. customThe liquid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-74597d26d1874c43a38f041140605bdb
Source dataset
uspto-grants-2016_06
Patent number
US09368732B2

Reaction notes

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