Methyl 3,5-dihydroxybenzoate

67-56-1

99-10-5

2150-44-9

Methyl 3,5-dihydroxybenzoate was synthesized from methanol and 3,5-dihydroxybenzoic acid using the method described by Brouwer et al. The method was adapted for the metathesis synthesis of amino acid-based dendritic polymers, aiming at obtaining dendritic macromolecules with alkyne groups on the surface for 1,3-dipolar cycloaddition ("click") reactions with amino acid/peptide-derived azides. This was done as follows: first, 3,5-dihydroxymethylbenzoate (21.4 g, 130 mmol) was dissolved in anhydrous DMF (250 mL), followed by the addition of anhydrous K2CO3 (45 g, 330 mmol, 2.5 eq.). A toluene solution of propargyl bromide (35 mL, 314 mmol, 2.5 eq.) was added slowly and dropwise to this suspension. The reaction mixture was stirred continuously for 48 hours at room temperature. Upon completion of the reaction, DMF was removed by evaporation and the residue was redissolved in EtOAc (400 mL). The organic phase was washed sequentially with H2O (3 × 100 mL), KHSO4 (3 × 100 mL) and brine (3 × 100 mL), after which it was dried with Na2SO4 and evaporated under vacuum. The residue was recrystallized by EtOAc/hexane to afford the target product 1 as off-white crystals in 81% yield (25.2 g). The product was characterized by thin layer chromatography (TLC) and nuclear magnetic resonance (NMR): Rf (EtOAc/hexane 4:1 v/v): 0.76; Rf (DMC/MeOH 98:2 v/v): 0.87; Rf (CHCl3/MeOH/AcOH 95:20:3 v/v): 0.83; 1H-NMR (CDCl3) δ 2.55 (t, J=2.47Hz, 2H), 3.91 (s, 3H), 4.72 (d, J=2.47Hz, 4H), 6.81 (t, J=2.20Hz, 1H), 7.29 (d, J=2.20Hz, 2H); 13C-NMR (CDCl3) δ 52.4, 56.0, 76.0, 77.9, 107.5, 108.8, 132.0, 157.8, 158.4; elemental analysis results: C14H12O4, calculated value C 68.83, H 4.95, measured value C 68.76, H 4.95.