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

Temperatur

75 °C

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).

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)

ORD-Eintrag

ord-91c4804d62f74640890f95bb70d12ceb

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08450522B2