Potassium Carbonate → Methyl 2'-ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylate

Temperature

100 °C

To a solution of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1 Step 2, 12.0 g, 46.3 mmol) in toluene (150 mL) and water (35 mL) under N2, was added 2-ethylbenzene boronic acid (9.02 g, 60.1 mmol) followed by potassium carbonate (19 g, 139 mmol) and Pd(PPh3)4 (2.67 g, 2.31 mmol). The reaction mixture was degassed with N2 and heated at 100° C. for 12 hours. The reaction mixture was diluted with EtOAc. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate (100 mL), water (2×100 mL) and brine (100 mL). It was then dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by chromatography (silica gel, pet ether/EtOAc) to afford the title compound as a pale yellow liquid (12.0 g, 83%). 1H NMR (CDCl3, 400 MHz) δ 8.25 (1H, s), 8.00 (1H, d), 7.35 (2H, m), 7.25 (2H, m), 7.08 (1H, d), 4.12-4.21 (2H, m), 3.94 (3H, s), 3.29 (3H, s), 2.28-2.43 (2H, m), 1.03 (3H, t).

1. customThe reaction mixture was degassed with N2
2. additionThe reaction mixture was diluted with EtOAc
3. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate (100 mL), water (2×100 mL) and brine (100 mL)
4. dry with materialIt was then dried over sodium sulphate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by chromatography (silica gel, pet ether/EtOAc)

ORD record

ord-d3f34a66e203473cbe81b7be6f14f4bd

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815919B2