Benzyl step 3,4-bis-(benzyloxy)benzoate (13): Compound thirteen try synthesized depending on the general process using step 3,4-dihydroxybenzoic acidic (5

General processes: To help you a suspension system of your own suitable benzyl benzoates (12–14) during the EtOH at room-temperature try additional too much 5 Yards NaOH provider plus the ensuing combination encouraged not as much as reflux having 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).

Therefore

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), kinkyads yorumlar 6.86 (d, J=8.4 Hz, 1H), 3.91 (s, 6H), 3.87 (s, 3H).

Preparation regarding benzoic acids 16–18. The reaction mix was cooled off so you’re able to room-temperature and acidified to help you pH 3 of the dropwise inclusion out-of 12 Yards HCl. The fresh new resulting precipitate was blocked from, washed having liquid and you may dehydrated below quicker stress to pay for the fresh new relevant 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), 5.20 (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).