2,5-Dihydroxybenzoic acid → 5-(2,6-Dimethyl-4-nitrophenoxy)-2-(2-methoxyethoxymethoxy)benzoic acid 2-methoxyethoxymethyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of sodium NaH (60% dispersion in mineral oil; 1.32 g, 33 mmol) in 50 mL of NMP is cooled to 0° C. and 2,5-dihydroxybenzoic acid (1.54 g, 10 mmol) is added in one portion. The mixture is warmed to room temperature, and after 30 min, 4-chloro-3,5-dimethyl-nitrobenzene (2.41 g, 13 mmol) is added in one portion and the reaction is heated at 120° C. for 3 h. The reaction is cooled to RT and 2-methoxyethoxymethyl chloride (2.85 mL, 25 mmol) is added. After stirring for 30 min, the mixture is poured onto water and the product is taken up in Et2O. The organic solution is washed with brine, dried over anhydrous Na2SO4 and concentrated. Chromatography on silica (eluant; EtOAc/hexane-1/2→3/2) affords 5-(2,6-dimethyl-4-nitrophenoxy)-2-(2-methoxyethoxymethoxy)benzoic acid 2-methoxyethoxymethyl ester: NMR (CDCl3) 2.23 (s, 6H), 3.36 (s, 3H), 3.38 (s, 3H), 3.54-3.60 (m, 4H); 3.80-3.90 (m, 4H), 5.28 (s, 2H), 5.52 (s, 2H), 6.82 (dd, 1H, J=9,3), 7.17-7.23 (m, 2H), 8.02 (s, 2H).

Provenance & Evidence