3,4-BIS(BENZYLOXY)BENZOICACID

C) 3, 4-Dibenzyloxy benzoic acid; A solution of sodium hydroxide (1.2 g) in methanol (100 ml) was added to a solution of 3, 4-dibenzyloxy benzoic acid methyl ester (4.64 g) in methanol (50 ml) and refluxed for 4 hrs. After removal of methanol under reduced pressure the residue was dissolved in water (100 ml) and washed with ethyl acetate (2 x 50 ml). The aqueous layer was acidified with 2N hydrochloric acid to pH 2. The precipitated product was collected by filtration which on drying under vacuum provided 2.4 g of 3, 4-benzyloxy benzoic acid. (Yield = 74percent) 'H NMR CDC13 7.7 (2H, b, s) 7.27-7.5 (10H, m) 6.98 (lH, d, J 8Hz) 5.26 (2H, s) 5.22 (2H, s)To a solution of 8b (15.0 g, 97.4 mmol) in MeOH (360 mL) was added SOCl2 (7.9 mL, 48.7 mmol) fordropwise at 60 °C. The reaction mixture was stirred at 60 °C for 10 h. Then, the reaction mixture wasevaporated under reduced pressure. The crude mixture was applied to following reaction without furtherpurification.To a mixture of crude residue and K2CO3 (40.4 g, 0.292 mol) in DMF (162 mL) was added benzylbromide (29.0 mL, 0.244 mol) at 100 °C. The reaction mixture was stirred at 100 °C for 16 h. Then, thereaction mixture was filtered through a pad of Celite, diluted with H2O, and extracted with EtOAc. Theorganic layer was washed with water and brine, dried over anhydrous MgSO4, and evaporated underreduced pressure. The crude mixture was applied to following reaction without further purification.To a stirred solution of crude residue in MeOH/THF (1/1, 324 mL) were added 4 M NaOH aq. (85 mL, 0.34 mol) at 80 °C. The reaction mixture was stirred at same temperature for 1 h. Then, the reactionmixture was quenched with 6 M HCl aq., filtered and washed with H2O to give 9b (32.2 g, 96.3 mmol, 99percent) as a white solid.Spectral data for 9b were in good agreement with those reported in reference.16General procedure: A solution of hydroxy benzoic acid (1.0 equiv), BnBr (3-5 equiv) and K(B) 3, 4-Dibenzyloxybenzoic Acid (b) (Second step) Stirrer, And a reaction vessel equipped with a thermometer, 20 g (55 mmol) of the compound represented by formula (S-1), Sodium hydroxide 5.3 g (132 mmol), ethanol 200 ml, Add 50 ml of pure water, Hydrolysis was performed by stirring at 60 C. for 2 hours.After the reaction is completeA 10% aqueous hydrochloric acid solution was added to neutralize the reaction solution.After cooling the reaction solution, the precipitated crystals are filtered, The crystals were washed with water and ethanol and dried.Further, 18 g (53 mmol) of 3, 4-dibenzyloxybenzoic acid obtained was added to a stirrer, Charge into a reaction vessel equipped with a cooler and thermometer, Furthermore, 3.7 g (27 mmol) of 2- (4-hydroxyphenyl) ethanol, 610 mg of dimethylaminopyridine, 200 ml of methylene chloride was charged.Keep the reaction vessel at 5 C or below with an ice-cooled bath.In an atmosphere of nitrogen gas, 8 g (63 mmol) of diisopropylcarbodiimide was slowly added dropwise. After completion of dropping, the reaction vessel was returned to room temperature and reacted for 5 hours. After the reaction solution was filtered, 200 ml of methylene chloride was added to the filtrate, washed with a 10% aqueous hydrochloric acid solution, further washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified with a double amount (weight ratio) silica gel column and recrystallized with methylene chloride / methanol to obtain 17.7 g of a compound represented by the formula (S-3).

Molecular Weight:334.4
XLogP3:4.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:7
Exact Mass:334.12050905
Monoisotopic Mass:334.12050905
Topological Polar Surface Area:55.8
Heavy Atom Count:25
Complexity:399
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes