Sodium Carbonate → Benzyl 3-fluoro-2'-hydroxybiphenyl-4-carboxylate

HRID 1026557Notes

Reaction equation

HRID 1026557 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[C:4]([F:18])[CH:3]=1.[OH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[F:18][C:4]1[CH:3]=[C:2]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[OH:19])[CH:17]=[CH:16][C:5]=1[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2773454(2-Hydroxyphenyl)boronic acidHCID 22351348Benzyl 4-bromo-2-fluorobenzoate

Product 1

HCID 68005717Benzyl 3-fluoro-2'-hydroxybiphenyl-4-carboxylateYield 89.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixed solvent solution of benzyl 4-bromo-2-fluorobenzoate (67.0 g) and 2-hydroxyphenylboronic acid (31.3 g) in 1,2-dimethoxyethane (750 ml) and water (250 ml) were added sodium carbonate (68.7 g) and tetrakis(triphenylphosphine)palladium (12.5 g), followed by stirring under heating at reflux for 5 hours. The reaction solution was brought back to room temperature, and then poured into ice water, followed by extraction with ethyl acetate. The organic layer was washed sequentially with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography, and further washed with hexane to afford benzyl 3-fluoro-2′-hydroxybiphenyl-4-carboxylate (62.5 g).

Workup

  1. temperatureunder heating
  2. temperatureat reflux for 5 hours
  3. customwas brought back to room temperature
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed sequentially with water and saturated sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography
  9. washfurther washed with hexane

Sources & evidence

ORD record
ord-59723858dcb4484aa86762041e211582
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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