Potassium Phosphate, Tribasic → Methyl 3'-((difluoromethyl)oxy)-2-(2,2-dimethylcyclopentyl)-1,1'-biphenyl-4-carboxylate

温度

75 °C

A stirred mixture of 66.11F (0.48 g, 1.26 mmol), ground S-Phos (104.8 mg, 0.255 mmol), palladium acetate (29.1 mg, 0.130 mmol), and potassium phosphate tribasic (0.6727 g, 3.17 mmol) in dry DMF (5.0 mL) was purged with argon and placed under vacuum (repeated three times). Before heating, 66.11B (0.512 g, 1.89 mmol) was added via syringe, and then the mixture was heated to 75° C. After 16 hours, the reaction was cooled to room temperature, diluted with water and extracted three times with EtOAc. The combined organic layers were washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified on silica gel (0-20% EtOAc in hexanes) to yield 66.11G as a colorless oil (308.9 mg, 65%). 1H NMR (500 MHz, CDCl3) δ ppm 8.11 (1H, d, J=1.7 Hz), 7.90 (1H, dd, J=7.9, 1.8 Hz), 7.44 (1H, m), 7.28 (1H, m), 7.16 (2H, m), 7.07 (1H, s), 6.57 (1H, t, J=75 Hz), 3.97 (3H, s), 3.10 (1H, t, J=9.4 Hz), 2.13 (2H, m), 1.90 (1H, m), 1.73 (1H, m), 1.61 (1H, m), 1.38 (1H, ddd, J=12.6, 9.4, 7.6 Hz), 0.75 (3H, s), 0.58 (3H, s).

1. customwas purged with argon
2. temperatureBefore heating
3. temperaturethe reaction was cooled to room temperature
4. extractionextracted three times with EtOAc
5. washThe combined organic layers were washed 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 on silica gel (0-20% EtOAc in hexanes)

ORDレコード

ord-354e677e080e4b54a411cb4575bd86f1

出典データセット

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08030354B2