Benzyl step step three,cuatro-bis-(benzyloxy)benzoate (13): Compound 13 was synthesized with respect to the standard process having fun with step 3,4-dihydroxybenzoic acidic (5

Standard process: So you can a suspension of your own appropriate benzyl benzoates (12–14) into the EtOH at the room-temperature is actually extra too much 5 Yards NaOH services together with ensuing mix empowered lower than reflux for 8 h

00 g, 32.5 mmol) and was obtained as a pale yellow solid (7.80 g, mmol, 57 %). 1 H NMR (400 MHz, CDCl₃): ?=7.71–7.six5 (m, 2H), 7.49–7.31 (m, 15H), 6.93 (d, J=8.9 Hz, 1H), 5.32 (s, 2H), 5.22 (s, 2H), 5.20 (s, 2H).

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Benzyl 3,5-bis-(benzyloxy)benzoate (14): Compound 14 was synthesized according to the general procedure (without NaI) by using 3,5-dihydroxybenzoic acid (0.77 g, 5 mmol) and was obtained as a pale yellow solid (0.41 g, 0.95 mmol, 19 %). 1 H NMR (500 MHz, [D₆]DM): ?=7.46–7.31 (m, 15H), 7.18 (s, 2H), 6.98 (s, 1H), 5.33 (s, 2H), 5.15 (s, 4H).

Methyl 3,4-dimethoxy-benzoate (15): To a solution of 3,4-dihydroxy-benzoic acid (0.80 g, 5.2 mmol, 1 equiv) in DMF (30 mL) was added methyl iodide (1.50 mL, 25 mmol, 5 equiv) and potassium carbonate (3.59 g, 25 mmol, 5 equiv) at room temperature. The mixture was stirred at 50 °C for 16 h, cooled to room temperature and concentrated under reduced pressure. Water was added and the resulting mixture extracted with EtOAc (3?20 mL). The combined organic layers were dried over anhydrous Na₂₄ and filtered. The EtOAc was evaporated under reduced pressure and the resulting crude product purified by column chromatography on SiO₂ (hexane/EtOAc as eluent) to afford 15 as a white solid (0.73 g, 3.74 mmol, 72 %). 1 H NMR (400 MHz, CDCl₃): ?=7.65 (d, J=8.4 Hz, 1H), 7.52 (s, 1H), 6.86 (d, J=8.4 Hz, 1H), 3.91 (s, 6H), 3.87 (s, 3H).

Preparing off benzoic acids 16–18. The fresh response combination was cooled to help you room-temperature and you may acidified to help you pH step three by the dropwise inclusion of 12 Meters HCl. The resulting precipitate is actually filtered from, clean which have drinking water and you will dried around shorter tension to afford brand new related acids sixteen–18.

2,4-Bis-(benzyloxy)benzoic acid (16): Compound 16 was synthesized according to the general procedure, using 12 (1.01 g, 2.36 mmol). The resulting precipitate was recrystallized from MeOH/CH₂Cl₂ (50 : 1) and afforded 16 as a white solid (0.80 g, 1,89 mmol, 80 %). 1 H NMR (400 MHz, [D₆]DM): ?= (s, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.54–7.27 (m, 10H), 6.82 (s, 1H), 6.67 (d, J=8.8 Hz, 1H), 5 squirt giriÅŸ.20 (s, 2H), 5.16 (s, 2H).

3,4-Bis-(benzyloxy)benzoic acid (17): Compound 17 was synthesized according to the general procedure, using 13 (2.30 g, 5.42 mmol) and was obtained as a white solid (1.70 g, 5.09 mmol, 94 %). 1 H NMR (400 MHz, [D₆]DM): ?= (s, 1H), 7.46 (s, 1H), 7.45 (d, J=7.4 Hz, 1H), 7.39–7.19 (m, 10H), 7.06 (d, J=8.8 Hz, 1H), 5.12 (s, 2H), 5.08 (s, 2H).

3,5-Bis-(benzyloxy)benzoic acid (18): Compound 18 was synthesized according to the general procedure, using 14 (0.21 g, 0.50 mmol) and was obtained as a white solid comprising a mixture of acid and sodium salt (0.21 g, quant.). 1 H NMR (500 MHz, [D₆]DM): ?= (s, 1H) 7.46–7.32 (m, 10H), 7.16 (s, 2H), 6.93 (s, 1H), 5.14 (s, 4H).

Preparation of 3,4-dimethoxy-benzoic acid (19): To a suspension of 15 (0.35 g, 1,79 mmol, 1 equiv) in H₂O/MeOH (1 : 1 v/v, 30 mL) at room temperature was added LiOH monohydrate (0.23 g, 5.36 mmol, 3 equiv) and the resulting mixture stirred for 4 h. The reaction mixture was then brought to pH 3 using 1 M HCl and extracted with EtOAc. The combined organic layers were dried over anhydrous Na₂₄ and filtered. The EtOAc was evaporated under reduced pressure to afford 19 as a white solid (0.31 g, 1.70 mmol, 95 %). 1 H NMR (400 MHz, [D₆]DM): ?= (s, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.44 (s, 1H), 7.03 (d, J=8.5 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H).