Water → HCID 57467625, compound

HRID 1662402Notes

Reaction equation

HRID 1662402 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].CO[C:21]1C=CC=[C:25](OC)[C:26]=1[C:27]1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C=O)C.O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:25][C:26]([CH3:27])=[CH:21][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]

Participants

7

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57467623Methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

Product 1

HCID 57467625HCID 57467625, compoundYield 495.1%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoate 66.6F (0.500 g, 1.6 mmol), palladium acetate (0.036 g, 0.16 mmol), S-Phos (0.13 g, 0.32 mmol) and tripotassium phosphate (0.32 mL, 4.0 mmol) in DMF (10.00 mL, 129 mmol) and water (0.40 mL, 22 mmol) was stirred. The mixture was purged with nitrogen and placed under vacuum and the process repeated three times. Before heating, 2-methylprop-1-enylboronic acid (0.24 g, 2.4 mmol, commercially available from Synthonix, Cat. No. D3007G1) was added, and the mixture was heated to 70° C. and stirred for 23 hours. The mixture was then cooled to room temperature, diluted with brine, 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 (0-10% EtOAc in hexanes) to yield 66.20A as a colorless oil (0.460 g, 100% yield).

Workup

  1. customThe mixture was purged with nitrogen
  2. temperatureBefore heating
  3. additionD3007G1) was added
  4. stirringstirred for 23 hours
  5. temperatureThe mixture was then cooled to room temperature
  6. additiondiluted with brine
  7. extractionextracted three times with EtOAc
  8. dry with materialAfter drying over anhydrous magnesium sulfate
  9. filtrationfiltering
  10. customthe organic solvent was removed under reduced pressure
  11. customthe product was then purified on silica gel (0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-925ae6489df54c44b2ab658f8d4b584d
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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