4.2.4. Preparation of methyl 5-((3,7-dihydroxy-1-methyl-6-oxo-6H-benzo[c]chromen-9-yl)oxy)pentanoate (8)

A 3 M solution of HCl in MeOH (150 µL, 0.450 mmol) was added to a solution of biaryl compound 7 (26.1 mg, 0.050 mmol) in anhydrous MeOH (1.5 mL) and the reaction mixture was stirred at rt for 22 h. After concentration under vacuum, the residue was dissolved in anhydrous CH₂Cl₂ (4 mL) and treated with trifluoroacetic acid (430 µL). Following stirring for 20 h at rt, thin layer chromatography showed the formation of a single compound and all the volatiles were removed under vacuum, using CHCl₃ to co-evaporate the last traces of TFA. The obtained residue was purified by chromatography, using CHCl₃ as eluent, to give benzochromenone derivative 8 (18.1 mg, 97%) as a white solid. ¹H NMR (300 MHz, DMSO-d₆) δ 11.79 and 10.33 (each s, 1H each, 2×OH), 7.13 (d, J = 2.2 Hz, 1H, H-10), 6.69 (d, J = 2.6 Hz, 1H, H-2), 6.61 (d, J = 2.6 Hz, 1H, H-4), 6.55 (d, J = 2.2 Hz, 1H, H-8), 4.11 (t, J = 5.9 Hz, 2H, H₂-5), 3.59 (s, 3H, OCH₃), 2.68 (s, 3H, CH₃), 2.41 (t, J = 7.0 Hz, 2H, H₂-2), 1.85–1.56 (m, 4H, H₂-3 and H₂-4); ¹³C NMR (75 MHz, DMSO-d₆) δ 173.2 (CO₂CH₃), 165.5 (CO), 164.6 (C-9), 164.1 (C-7), 158.5 (C-3), 152.6 (C-4a), 138.4 (C-1), 137.7 (C-10a), 117.5 (CH₂-2), 108.8 (C-10b), 103.6 (CH-10), 101.6 (CH-4), 99.5 (CH-8), 98.3 (C-6a), 67.8 (CH₂-5), 51.2 (CO₂CH₃), 32.8 (CH₂-2), 27.8 (CH₂-4), 25.0 (CH₃), 21.1 (C-3); HRMS (TOF, ES+) m/z calculated for C₂₀H₂₁O₇ [M + H]⁺ 373.1282; found 373.1278.