Water → Methyl 3-(3,6-dihydro-2H-pyran-4-yl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 66.6 F (1.40 g, 4.45 mmol), ground S-Phos (0.38 g, 0.920 mmol), palladium acetate (0.11 g, 0.475 mmol), 66.46B (1.40 g, 6.65 mmol), and potassium phosphate tribasic (2.48 g, 11.7 mmol) in DMF (10.0 mL) and water (0.5 mL) was purged three times with argon. The mixture was heated to 75° C. and monitored with LC-MS. After 21 hours, the reaction was cooled to room temperature and then 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 on silica gel using 0-20% EtOAc in hexanes to afford 66.46C as a colorless oil (0.73 g, 52% yield). MS ESI (pos.) m/e: 340.9 (M+Na)+.

Provenance & Evidence