5-Bromosalicylic acid → 3'-Chloro-4'-fluoro-4-hydroxy-biphenyl-3-carboxylic acid

HRID 2373782Notes

Reaction equation

HRID 2373782 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].Br[C:13]1[CH:14]=[CH:15][C:16]([OH:22])=[C:17]([CH:21]=1)[C:18]([OH:20])=[O:19].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[CH:15][C:16]([OH:22])=[C:17]([C:18]([OH:20])=[O:19])[CH:21]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 3

HCID 69725-Bromosalicylic acidHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 219213173'-Chloro-4'-fluoro-4-hydroxy-biphenyl-3-carboxylic acidYield 43.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

3-Chloro-4-fluoro-phenylboronic acid (3.2 g, 18.4 mmol), 5-bromo-2-hydroxy-benzoic acid (4.0 g, 18.4 mmol), and Pd (PPh3)4 (1.67 g, 1.84 mmol) were dissolved in 250 mL of DME, a 1 M Na2CO3 solution (46 mL, 46.0 mmol) added and the mixture heated to 80° C. for 20 h. The reaction mixture was filtered, partially evaporated and EtOAc (200 mL) and 1 N HCl (100 mL) added. The organic layer washed with 1N HCl and saturated sodium bicarbonate, dried over sodium sulfate, and evaporated. The crude material was filtered through a silica plug (THF) to give 3′-chloro-4′-fluoro-4-hydroxy-biphenyl-3-carboxylic acid (2.15 g).

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompartially evaporated
  3. additionEtOAc (200 mL) and 1 N HCl (100 mL) added
  4. washThe organic layer washed with 1N HCl and saturated sodium bicarbonate
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. filtrationThe crude material was filtered through a silica plug (THF)

Sources & evidence

ORD record
ord-90c5c581e3844ef390a161f7f73dad68
Source dataset
uspto-grants-2008_12
Patent number
US07459472B2

Reaction notes

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