Sodium Chloride → 3-(6-Methoxypyridin-2-yl)thiophene-2-carbaldehyde

HRID 1917472Notes

Reaction equation

HRID 1917472 reaction equation
[CH:1]([C:3]1[S:4][CH:5]=[CH:6][C:7]=1B(O)O)=[O:2].Br[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[N:13]=1.C(=O)([O-])[O-].[Na+].[Na+].[Na+].[Cl-]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO.C1(C)C=CC=CC=1>[CH3:19][O:18][C:14]1[N:13]=[C:12]([C:7]2[CH:6]=[CH:5][S:4][C:3]=2[CH:1]=[O:2])[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 2568102-Bromo-6-methoxypyridineHCID 27734262-Formyl-3-thiopheneboronic acid

Product 1

HCID 579992833-(6-Methoxypyridin-2-yl)thiophene-2-carbaldehyde

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a 500 mL flask was added 2-formylthiophene-3-boronic acid (30A, 5.00 g, 32.1 mmol, 1.0 eq.), 2-bromo-6-methoxypyridine (30B, 6.03 g, 32.1 mmol, 1.0 eq.), toluene (100 mL), EtOH (100 mL), aqueous sodium carbonate (2N, 32 ml, 64 mmol, 2.0 eq.), and Pd(dppf)Cl2 (1.17 g, 1.6 mmol, 0.05 eq.). The reaction was stirred overnight at 90° C. The reaction was cooled and saturated aqueous NaCl (100 mL) was added and the mixture was stirred for 20 min. The reaction mixture was extracted with EtOAc (2×100 mL) and the resulting organic layers were combined and passed through a Celite pad to remove residual Pd. The organic phases were washed with a succession of H2O (100 mL) and saturated aqueous NaCl (100 mL) and then dried over anhydrous Na2SO4, filtered, and concentrated to give a bubbly brown solid that was used in the next step without further purification (6.2 g, 88%). ESI-MS: m/z 220.2 (M+H)+.

Workup

  1. temperatureThe reaction was cooled
  2. stirringthe mixture was stirred for 20 min
  3. extractionThe reaction mixture was extracted with EtOAc (2×100 mL)
  4. customto remove residual Pd
  5. washThe organic phases were washed with a succession of H2O (100 mL) and saturated aqueous NaCl (100 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a bubbly brown solid that
  10. customwas used in the next step without further purification (6.2 g, 88%)

Sources & evidence

ORD record
ord-04f4d0df2d1f4bedabcdf0aafd0db4e2
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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