N#N.[CH2:3]([O:5][C:6](=[O:29])[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:28])[CH2:15][C:16]2[CH:21]=[C:20]([O:22]C)[C:19]([O:24]C)=[C:18]([O:26]C)[CH:17]=2)[CH2:10][CH2:9]1)[CH3:4].B(Br)(Br)Br.O>C(Cl)Cl>[CH2:3]([O:5][C:6](=[O:29])[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:28])[CH2:15][C:16]2[CH:21]=[C:20]([OH:22])[C:19]([OH:24])=[C:18]([OH:26])[CH:17]=2)[CH2:10][CH2:9]1)[CH3:4](The following reaction is done in an anhydrous N2 atmosphere.) Dissolve {4-[2-(3,4,5-Trimethoxy-phenyl)-acetyl]-piperazin-1-yl}-acetic acid ethyl ester (64) (99 mg, 0.26 mmol) in anhydrous DCM (6.0 mL), cool the solution to −78° C. and add dropwise a 1 M BBr3 solution in DCM (2.30 mL, 2.30=101). Stir the reaction mixture for 30 min at −78° C. and after slowly warming up for additional 4 h at −20° C. Add dropwise water and extract the mixture with EtOAc (3 times). Wash the combined organic layer with brine and dry it dry with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain {4-[2-(3,4,5-Trihydroxy-phenyl)-acetyl]-piperazin-1-yl}-acetic acid ethyl ester (65) (34 mg, 40%) as a sticky brownish solid. 1H NMR (400 MHz, CD3OD): 1.35 (t, 3H, J=7.1 Hz); 3.14-3.24 (br.m, 2H); ca. 3.32 (br.m, 2H); 3.65 (s, 2H); 3.78-4.00 (br.m, 4H); 4.12 (s, 2H); 4.34 (q, 2H, J=7.1 Hz); 6.29 (s, 2H).
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