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

Standard processes: In order to a suspension of compatible benzyl benzoates (12–14) into the EtOH in the room temperature try extra an excess of 5 M NaOH services plus the resulting mixture empowered significantly less than reflux to possess 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), 6.86 (d, J=8.4 Hz, 1H), 3.91 (s, 6H), 3.87 (s, 3H).

Preparation of benzoic acids 16–18. The latest impulse combination try cooled off to room temperature and you can acidified to pH step three because of the dropwise inclusion from a dozen M HCl. The fresh new ensuing precipitate is filtered out of, wash having liquid and you can dehydrated lower than shorter pressure to pay for the latest associated 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) mylol ücretsiz uygulama, 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).