Water → Methyl 2'-(difluoromethyl)-2-methylbiphenyl-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (Combiblocks PN-8756, 1.86 g, 6.74 mmol), 1-bromo-2-difluoromethyl-benzene (Fluorochem 023878, 1.67 g, 8.08 mmol), cesium fluoride (3.07 g, 20.2 mmol) and PdCl2(PPh3)2 (142 mg, 0.20 mmol) was prepared in dioxane (20 mL) and water (10 mL) under nitrogen atmosphere. The resulting mixture was heated at 90° C. for 2 hours. The reaction mixture was diluted with MTBE (60 mL), and then washed with water (2×50 mL) and brine (50 mL). The aqueous layers were extracted with MTBE (50 mL). The organic layers were combined, dried (MgSO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, DCM/heptane), the title compound was obtained as a colorless oil (1.42 g, 76%). HPLC (Method A) Rt 5.0 min (purity: 99.1%). 1H NMR (DMSO-d6, 300 MHz) δ 7.93 (s, 1H), 7.84 (dd, J=7.9, 1.4 Hz, 1H), 7.75 (m, 1H), 7.67-7.56 (m, 2H), 7.28 (m, 2H), 6.55 (t, J=54.7 Hz, 1H), 3.88 (s, 3H), 2.06 (s, 3H).

Provenance & Evidence