Ethanol → 4-Pyridin-2-ylbenzaldehyde

HRID 1909351Notes

Reaction equation

HRID 1909351 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)=[O:2].Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.C(O)C.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:6]1[CH:7]=[CH:8][C:3]([CH:1]=[O:2])=[CH:4][CH:5]=1

Participants

7

Reactant 4

HCID 702Ethanol2×HCID 79732-BromopyridineHCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic Acid

Product 1

HCID 15152404-Pyridin-2-ylbenzaldehydeYield 68.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
77 °C

Procedure

A mixture of 4-formyl-phenylboronic acid (5.0 g, 33.0 mmol) and 2-bromopyridine (5.53 g, 35.0 mmol, 1.05 equiv.) in 265 mL of 4:3 toluene/95% ethanol was degassed with nitrogen for 30 minutes and then heated under a nitrogen atmosphere, resulting in a clear solution. A slurry of Pd(PPh3)4 (0.77 g) in 50 mL of a 4:4 mixture of toluene and 95% ethanol was added, followed by 50 mL of 3M aqueous Na2CO3. The resulting mixture was gently refluxed at 77° C. After 16 hours, the reaction mixture was cooled to room temperature, and the solid removed by filtration. The filtrate was transferred to a separatory funnel, and the layers separated. The aqueous layer was extracted with toluene (3×50 mL). The combined organics were washed with water, then saturated sodium chloride, and dried over sodium sulfate. The solution was filtered, and the filtrate concentrated under reduced pressure to give a yellow oil. Purification by Biotage chromatography (40+M cartridge; gradient, 0 to 5% methanol/dichloromethane) gave 4.13 g (68%) of (3) as a light-yellow solid. TLC Rf (hexane/ethyl acetate, 2:1)=0.25; 1H NMR (CDCl3) δ 10.1 (s, HCO), 8.77 (d, 1H), 8.20 (d, 2H), 8.00 (d, 2H), 7.81 (m, 2H), 7.31 (q, 1H); MS (M)+=184; HPLC tR 1.2 minutes.

Workup

  1. customwas degassed with nitrogen for 30 minutes
  2. temperatureheated under a nitrogen atmosphere
  3. customresulting in a clear solution
  4. additionwas added
  5. temperaturethe reaction mixture was cooled to room temperature
  6. customthe solid removed by filtration
  7. customThe filtrate was transferred to a separatory funnel
  8. customthe layers separated
  9. extractionThe aqueous layer was extracted with toluene (3×50 mL)
  10. washThe combined organics were washed with water
  11. dry with materialsaturated sodium chloride, and dried over sodium sulfate
  12. filtrationThe solution was filtered
  13. concentrationthe filtrate concentrated under reduced pressure
  14. customto give a yellow oil
  15. customPurification by Biotage chromatography (40+M cartridge; gradient, 0 to 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-c4f615e4b3a4481db411d53bb70c458d
Source dataset
uspto-grants-2013_12
Patent number
US08598364B2

Reaction notes

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