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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence