Sodium Carbonate → 3-(Pyridin-3-yl)phenol

HRID 1269490Notes

Reaction equation

HRID 1269490 reaction equation
C(B(CC)[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)C.Br[C:13]1[CH:14]=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.C(O)C.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>[N:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:13]2[CH:14]=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=2)[CH:5]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 115633-BromophenolHCID 6428513-(Diethylboryl)pyridine

Product 1

HCID 129379483-(Pyridin-3-yl)phenolYield 92%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

A mixture of diethyl(3-pyridyl)borane (11.80 g, 80.0 mmol), 3-bromophenol (16.60 g, 96.0 mmol), Pd(PPh3)4 (0.92 g, 0.80 mmol), and Na2CO3 (17.0 g, 160.0 mmol) in toluene/water/ethanol (160/80/40 mL) was purged with nitrogen for 5 min and then heated at reflux under nitrogen for 2 h. After solvent removal, the aqueous residue was partitioned between ethyl acetate/brine (400/250 mL). The separated organic layer was washed with brine, filtered, and concentrated. The solid residue was taken up in 130 mL of 3 M HCl, stirred for 15 min, diluted with brine (150 mL), and extracted with ethyl acetate (2×250 mL). The separated aqueous layer was cooled in ice/water bath, adjusted to pH 10 with solid NaOH and Na2CO3, and extracted with ethyl acetate (2×300 mL). The organic extract was dried over sodium sulfate and concentrated to give 12.60 g (92%) of 3-pyridin-3-yl-phenol as a light yellow solid: 1H NMR (CDCl3) δ 6.99 (m, 1H), 7.08 (m, 1H), 7.22 (m, 1H), 7.36 (m, 1H), 7.43 (m, 1H), 8.00 (dd, 1H), 8.60 (d, 1H), 9.00 (s, 1H); MS m/z (relative intensity) 171 (M+, 100), 142 (17), 115 (21).

Workup

  1. customwas purged with nitrogen for 5 min
  2. temperatureheated
  3. temperatureat reflux under nitrogen for 2 h
  4. customAfter solvent removal
  5. customthe aqueous residue was partitioned between ethyl acetate/brine (400/250 mL)
  6. washThe separated organic layer was washed with brine
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additiondiluted with brine (150 mL)
  10. extractionextracted with ethyl acetate (2×250 mL)
  11. temperatureThe separated aqueous layer was cooled in ice/water bath
  12. extractionextracted with ethyl acetate (2×300 mL)
  13. extractionThe organic extract
  14. dry with materialwas dried over sodium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-0233f468e88d48089b63e721304a2793
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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