反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- -78 °C
PROCEDURE
实验过程
(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).
WORKUP
后处理
- custom(The following reaction
- temperatureAfter slowly warming up
- stirringstir the reaction solution for additional 4 h at rt
- temperatureCool
- customreaction mixture to 0° C.
- stirringunder vigorous stirring
- stirringto homogenize the mixture
- customPartition the hydrolized reaction mixture between water and EtOAc
- extractionextract the aqu
- washlayer with EtOAc (3×), wash
- dry with materialdry it with Na2SO4
- customPurify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95)