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

Participants

Reaction Conditions

Reaction Steps

(The following reaction is done in an N2 atmosphere.) To a solution of 2,3,4-Trimethoxyphenylboronic acid (32) (1.40 g, 6.60 mmol) in toluene (15.0 mL) is added EtOH (2.0 mL), Pd(PPh3)4 (208 mg, 0.18 mmol) and Na2CO3.10H2O (4.81 g, 16.80 mmol) in water (5.2 mL). The resulting mixture is carefully degassed (5 times alternating vacuum and flushing with N2). A solution of Methyl-3-bromobenzoate (9) (1.29 g, 6.00 mmol) in toluene (9.0 mL) is added by syringe, the resulting mixture is again carefully degassed and stirred 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, dry with Na2SO4 and remove solvent. Purify crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+5) to obtain 2′,3′,4′-Trimethoxy-biphenyl-3-carboxylic acid methyl ester (33) as a yellowish oil (1.07 g, 58%). 1H NMR (400 MHz, CDCl3): 3.66 (s, 3H); 3.89 (s, 3H); 3.92 (s, 6H); 6.74 (d, 1H, J=8.6 Hz); 7.03 (d, 1H, J=8.6 Hz); 7.44 (t, 1H, J=7.8 Hz); 7.70 (d, 1H, J=7.6 Hz); 7.97 (d, 1H, J=7.8 Hz); 8.15 (br.s 1H).

Provenance & Evidence