Nitrogen → 3',4',5'-Trimethoxy-biphenyl-2-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

(The following reaction is done in an N2 atmosphere.) To a solution of Methyl-2-bromobenzoate (53) (922 mg, 4.29 mmol) in toluene (11 mL) is added Pd(PPh3)4 (297 mg, 0.26 mmol) and Na2CO3.10H2O (3.43 g, 12.00 mmol) in water (3.8 mL). Degas the resulting mixture is carefully (5 times alternating vacuum and flushing with N2). Add a solution of 3,4,5-Trimethoxyphenylboronic acid (54) (1.00 g, 4.72 mmol) in toluene (10 mL) by syringe, degas the resulting mixture again carefully and stir the resulting mixture overnight at 100° C. Partition the mixture between brine/EtOAc (1+1), separate layers, extract the aqu. layer with EtOAc (3×), wash the combined organic layer with brine and dry with Na2SO4. Purify the crude product by flash chromatography (silica gel, EtOAc/CyH 1+7, later 1+5) to obtain 3′,4′,5′-Trimethoxy-biphenyl-2-carboxylic acid methyl ester (55) as a yellow solid (1.30 g, 99%). 1H NMR (400 MHz, CDCl3): 3.65 (s, 3H); 3.84 (s, 6H); 3.87 (s, 3H); 6.52 (s, 2H); 7.35-7.42 (m, 2H); 7.50 (t, 1H, J=8.0 Hz); 7.73 (d, 1H, J=8.0 Hz).

Provenance & Evidence