Benzyl step 3,cuatro-bis-(benzyloxy)benzoate (13): Material thirteen are synthesized depending on the standard processes having fun with 3,4-dihydroxybenzoic acidic (5

General procedure: To help you a suspension system of one’s suitable benzyl benzoates (12–14) for the EtOH within room-temperature is actually added too much 5 M NaOH services and the resulting mixture inspired around reflux to own 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).

Thus

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).

Thinking regarding benzoic acids 16–18. The newest reaction mix is actually cooled to room-temperature and you may acidified so you’re able to pH step three by dropwise addition away from several Yards HCl. The fresh ensuing precipitate try filtered out of, sparkling with h2o and you can dried around reduced tension to cover the latest related acids 16–18.

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), 5.20 (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) polyamory date hookup, 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).