Dimethylformamide → Methyl 3-(1-(1,1-dimethylethyl)ethenyl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

HRID 404355Notes

Reaction equation

HRID 404355 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)[C:5]([O:7][CH3:8])=[O:6].COC1C=CC=C(OC)[C:26]=1[C:27]1[CH:28]=[CH:29]C=C[C:32]=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:56]N(C=O)C>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:32][C:27]([C:28]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)[C:5]([O:7][CH3:8])=[O:6])=[CH2:29])([CH3:26])[CH3:56]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57467623Methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

Product 1

HCID 57467622Methyl 3-(1-(1,1-dimethylethyl)ethenyl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoateYield 490.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

A stirred solution of methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoate T3.2 (2.50 g, 7.9 mmol), palladium acetate (0.18 g, 0.79 mmol), S-Phos (0.65 g, 1.6 mmol), tripotassium phosphate (1.6 mL, 20 mmol) in DMF (15.00 mL, 194 mmol) and water (0.600 mL, 33 mmol) was purged 3 times with nitrogen and placed under vacuum and the process repeated three times. Before heating, T22.2 (2.0 g, 9.5 mmol) was added, and the mixture was heated to 70° C. and stirred for 19 hours. The resulting mixture was then cooled to room temperature, diluted with water and extracted three times with EtOAc. After drying over anhydrous magnesium sulfate and filtering, the organic solvent was removed under reduced pressure and the product was then purified on silica gel (0-20% EtOAc in hexanes) to yield T22.3 as a colorless oil (2.50 g, 99% yield).

Workup

  1. temperatureBefore heating
  2. additionT22.2 (2.0 g, 9.5 mmol) was added
  3. temperatureThe resulting mixture was then cooled to room temperature
  4. extractionextracted three times with EtOAc
  5. dry with materialAfter drying over anhydrous magnesium sulfate
  6. filtrationfiltering
  7. customthe organic solvent was removed under reduced pressure
  8. customthe product was then purified on silica gel (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1b873107f7e24b1b84943a6d8851ac72
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Reaction notes

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