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

온도

75 °C

A stirred mixture of 83.2C (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 vacuum and the process was repeated three times. Before heating, 2-(5,5-dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (66.6° C.) (8.96 g, 40.4 mmol) was added via syringe, and then the mixture was heated to 75° C. After 21 hours, the reaction was cooled to room temperature, diluted with water and extracted three times with EtOAc. The combined 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 83.2D (5.65 g, 52%) 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 기록

ord-9d69cec76a11452ea8db04cee6826041

출처 데이터셋

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08030354B2