Sodium Carbonate → 3-p-Tolyl-pyridine-2-carbaldehyde

HRID 1592388Notes

Reaction equation

HRID 1592388 reaction equation
Br[C:2]1[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1COCC1.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>[C:11]1([CH3:10])[CH:16]=[CH:15][C:14]([C:2]2[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 164142313-Bromopyridine-2-carbaldehyde

Product 1

HCID 772302663-p-Tolyl-pyridine-2-carbaldehydeYield 77%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 22732251Tetrahydrofuran dimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred degassed solution of 3-bromo-2-pyridinecarboxaldehyde (198 mg, 1.06 mmol) and 4-methylbenzene boronic acid (152 mg, 1.12 mmol) in DME/THF (3.5 mL, 2.5:1) were added a 2 M Na2CO3 solution (0.9 mL) and Pd(PPh3)4 (63 mg, 0.055 mmol). The reaction mixture was flushed with Ar and maintained under Ar while being heated at 90° C. overnight. The mixture was then cooled and diluted with EtOAc (40 mL) and brine (30 mL). The organic layer was washed with brine (1×30 mL), dried (Na2SO4), filtered and concentrated. Purification of the resultant oil by column chromatography with silica gel (Hexanes/EtOAc, 2:1) afforded 3-p-tolyl-pyridine-2-carbaldehyde (161 mg, 77%) as a yellow oil. 1H NMR (CDCl3) δ 2.43 (s, 3H), 7.25-7.28 (m, 4H), 7.53 (dd, 1H, J=9, 6 Hz), 7.79 (dd, 1H, J=9, 1 Hz), 8.80 (dd, J=3, 1 Hz), 10.09 (s, 1H).

Workup

  1. customThe reaction mixture was flushed with Ar
  2. temperaturemaintained under Ar
  3. temperatureThe mixture was then cooled
  4. additiondiluted with EtOAc (40 mL) and brine (30 mL)
  5. washThe organic layer was washed with brine (1×30 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the resultant oil by column chromatography with silica gel (Hexanes/EtOAc, 2:1)

Sources & evidence

ORD record
ord-d7f95c72902d45338af49bd65371baed
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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