Nitrogen → [5-(3-Nitro-phenyl)-thiophen-2-yl]acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

FR544 (The following reaction is carried out in an N2 atmosphere.) Dissolve Tetrakis-(triphenylphosphine)-palladium(0) (1.12 g, 0.97 mmol) and ester (43) (4.57 g, 19.44 mmol) in toluene (200 mL) and EtOH (20.0 mL), degas the reaction mixture carefully (5 times) and flush with N2. Add 3-nitrophenylboronic acid (3.57 g, 21.38 mmol) and a 3 M aqueous Na2CO3 solution (18.1 mL, 54.3 mmol), degas the reaction mixture again carefully (5 times) and flush with N2. Stir the mixture for 18 h at 100° C. Partition the reaction solution between EtOAc and water and extract the separated aqueous layer with EtOAc (3 times). Wash combined organic layer with brine and dry it with Na2SO4. Purify the obtained crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+5) to obtain [5-(3-nitro-phenyl)-thiophen-2-yl]acetic acid methyl ester (56) as a yellow solid (3.15 g, 58%). 1H NMR (400 MHz, CDCl3): 3.75 (s, 3H); 3.85 (s, 2H); 6.94 (br.d, 1H, J=3.8 Hz); 7.27 (d, 1H, J=3.8 Hz); 7.51 (t, 1H, J=8.0 Hz); 7.84 (ddd, 1H, J1=7.8 Hz, J2=1.5 Hz, J3=0.8 Hz); 8.08 (ddd, 1H, J1=8.3 Hz, J2=2.1 Hz, J3=1.0 Hz); 8.39 (t, 1H, J=1.9 Hz).

Provenance & Evidence