Potassium Phosphate, Tribasic → Methyl 3-(5,5-dimethylcyclopent-1-enyl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

HRID 2098908Notes

Reaction equation

HRID 2098908 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][CH:30]=[CH:31][C:32]=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(B2OC(C)(C)C(C)(C)O2)=CCC1>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:28][C:27]1([CH3:26])[C:32]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=2[O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[C:5]([O:7][CH3:8])=[O:6])=[CH:31][CH2:30][CH2:29]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574675872-(5,5-Dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57467623Methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

Product 1

HCID 57706119Methyl 3-(5,5-dimethylcyclopent-1-enyl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoateYield 80%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A stirred mixture of T6.6 (10.1 g, 31.9 mmol), grounded S-Phos (2.62 g, 6.39 mmol), palladium acetate (0.72 g, 3.2 mmol), and potassium phosphate, tribasic (17.0 g, 80.2 mmol) in DMF (70 mL) and water (3.5 mL) was purged three times with argon and placed under vacuum three times. Before heating, 2-(5,5-dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (T6.3) (8.50 g, 38.3 mmol) was added via syringe. The resulting mixture was then heated to 75° C. After 21 hours (black solution), the reaction was cooled to room temperature, diluted with water, and extracted three times with EtOAc. The organic layers were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtering, the organic solvent was removed under reduced pressure. The residue was purified on silica gel (0-20% EtOAc in hexanes) to yield T6.7 as a colorless oil that solidified (yield 80%). 1H NMR (400 MHz) (CDCl3) δ ppm 7.91 (1H, dd, J=8.6, 2.3 Hz), 7.74 (1H, d, J=2.3 Hz), 7.15 (1H, d, J=8.6 Hz), 5.55 (1H, t, J=2.3 Hz), 5.49 (1H, t, J=2.9 Hz), 3.88 (3H, s), 3.82 (1H, td, J=11.1, 2.9 Hz), 3.64 (1H, m), 2.43 (2H, td, J=7.0, 2.3 Hz), 1.92 (5H, m), 1.69 (1H, m), 1.61 (2H, m), 1.09 (6H, d, J=13.7 Hz).

Workup

  1. customwater (3.5 mL) was purged three times with argon
  2. temperatureBefore heating
  3. temperaturethe reaction was cooled to room temperature
  4. extractionextracted three times with EtOAc
  5. washwashed twice with brine
  6. dry with materialAfter drying over anhydrous sodium sulfate
  7. filtrationfiltering
  8. customthe organic solvent was removed under reduced pressure
  9. customThe residue was purified on silica gel (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-91c4804d62f74640890f95bb70d12ceb
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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