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

温度

75 °C

A stirred mixture of T22.3 (10.33 g, 31.0 mmol), ground S-Phos (2.55 g, 6.21 mmol), palladium acetate (0.70 g, 3.11 mmol), and potassium phosphate, tribasic (16.49 g, 77.7 mmol) in DMF (75 mL) and water (4 mL) was purged with argon and placed under vacuum and the process repeated three times. Before heating, 2-(5,5-dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (T6.3) (8.96 g, 40.4 mmol) was added via syringe. The mixture was then heated at 75° C. After 21 hours, 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 filtration, the organic solvent was removed under reduced pressure. The residue was purified by silica gel flash chromatography (0-10% EtOAc/hexane) to yield T22.4 (5.65 g, 52% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.63 (1H, d, J=8.6 Hz), 6.93 (1H, d, J=13.3 Hz), 5.55 (1H, t, J=2.3 Hz), 5.43 (1H, t, J=2.7 Hz), 3.90 (3H, s), 3.82 (1H, m), 3.67 (1H, m), 2.41 (2H, td, J=7.0, 2.3 Hz), 1.97 (5H, m), 1.79 (3H, m), 1.07 (6H, d, J=13.7 Hz).

1. customwater (4 mL) was purged 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 and filtration
7. customthe organic solvent was removed under reduced pressure
8. customThe residue was purified by silica gel flash chromatography (0-10% EtOAc/hexane)

ORDレコード

ord-86b7519694dd4c26a1cb2887c676492a

出典データセット

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08450522B2