Nitrogen → (5-{2-[(2',3',4'-Trihydroxy-biphenyl-3-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve (5-{2-[(2′,3′,4′-Trimethoxy-biphenyl-3-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester (47) (66 mg, 0.13 mmol) in anhydrous DCM (3.4 mL) at −78° C., add dropwise a 1M solution of BBr3 in DCM (1.05 mL, 1.05 mmol) and stir for additional 30 min at −78° C. After slowly warming up stir the reaction solution for additional 4 h at rt. Cool reaction mixture to 0° C., add dropwise water and DCM under vigorous stirring followed by MeOH to homogenize the mixture. Partition the hydrolized reaction mixture between water and EtOAc, extract the aqu. layer with EtOAc (3×), wash combined organic layer with brine and dry it with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain (5-{2-[(2′,3′,4′-Trihydroxy-biphenyl-3-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid (48) (8 mg, 13%) as a white solid and (5-{2-[(2′,3′,4′-Trihydroxy-biphenyl-3-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester (49) (14 mg, 23%) as a brown foam. 1H NMR (400 MHz, CD3OD) (48): 3.86 (s, 2H); 6.49 (d, 1H, J=8.6 Hz); 6.74 (d, 1H, J=8.6 Hz); 6.98 (d, 1H, J=3.0 Hz); 7.19 (d, 1H, J=3.3 Hz); 7.36 (t, 1H, J=7.6 Hz); 7.43 (t, 1H, J=7.6 Hz); 7.51 (t, 1H, J=7.8 Hz); 7.62 (d, 1H, J=7.8 Hz); 7.71-7.84 (m, 3 Hz); 8.08 (br.s 1H); (49): 3.66 (s, 3H); 3.88 (s, 2H); 6.49 (d, 1H, J=8.3 Hz); 6.74 (d, 1H, J=8.3 Hz); 6.97 (d, 1H, J=3.5 Hz); 7.19 (d, 1H, J=3.5 Hz); 7.36 (td, 1H, J1=7.6 Hz, J2=1.5 Hz); 7.43 (td, 1H, J1=7.6 Hz, J2=1.5 Hz); 7.51 (t, 1H, J=7.8 Hz); 7.62 (dd, 1H, J1=7.6 Hz, J2=1.5 Hz); 7.73 (d, 1H, J=7.8 Hz); 7.81 (Ψdd, 2H, J1=7.6 Hz, J2=1.5 Hz); 8.09 (br.s 1H).

Provenance & Evidence