Water → Methyl 4-hydroxy-[1,1'-biphenyl]-3-carboxylate

HRID 1765046Notes

Reaction equation

HRID 1765046 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[CH:13][C:14]([OH:21])=[C:15]([CH:20]=1)[C:16]([O:18][CH3:19])=[O:17].O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Pd].CCOCC>[OH:21][C:14]1[CH:13]=[CH:12][C:11]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17]

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 77683Methyl 5-bromosalicylate

Product 1

HCID 3312033Methyl 4-hydroxy-[1,1'-biphenyl]-3-carboxylateYield 56.2%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 167845palladium(II) acetateCatalystHCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of phenylboronic acid (1.34 g, 11.0 mmol) and methyl 5-bromo-2-hydroxybenzoate (2.42 g, 10.5 mmol) in acetone (25 ml) was treated with water (30 ml), followed by potassium carbonate (3.77 g, 27.3 mmol) and finally, palladium (II) acetate (0.16 g, 0.7 mmol). Upon addition of the palladium, the reaction mixture rapidly darkened. The reaction mixture was heated to reflux and stirred for 6 h. After cooling the dark mixture, ether (40 ml) was added, stirred vigorously and decanted. This extraction process was repeated an additional four times. The ethereal extracts were dried over sodium sulphate and evaporated in vacuo to give a yellow liquid. The crude product was dissolved in petrol and loaded onto a silica flash column. The column was eluted with petrol, followed by 5-10% ethyl acetate in petrol. The second product collected was evaporated in vacuo and then recrystallised from petrol to provide a white crystalline solid (1.35 g, 5.90 mmol, 56% yield). 1H NMR (200 MHz., d6-DMSO) δ 4.05 (3H, s); 7.20 (1H, m); 7.50-7.58 (3H, m)−; 7.74 (2H, m); 7.97 (1H, m); 8.13 (1H, m); 10.67 (1H, s, OH).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. additionwas added
  4. stirringstirred vigorously
  5. customdecanted
  6. dry with materialThe ethereal extracts were dried over sodium sulphate
  7. customevaporated in vacuo
  8. customto give a yellow liquid
  9. washThe column was eluted with petrol
  10. customThe second product collected
  11. customwas evaporated in vacuo
  12. customrecrystallised from petrol

Sources & evidence

ORD record
ord-b4fe4a89ca8e4e95a4360575ffe3bf46
Source dataset
uspto-grants-2007_06
Patent number
US07226918B2

Reaction notes

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