METHYL3,4,5-TRIS(BENZYLOXY)BENZOATE

White Solid

Potassium carbonate (63.31 g, 400 mmol) and benzyl bromide (59.47 mL, 500 mmol) were added to a solution of 3, 4, 5-trihydroxybenzoate methyl ester (compound 60) (18.41 g, 100 mmol) in DMF (70 mL). This reaction mixture was stirred at 120°C for seven hours, and then poured into water. The mixture was extracted with ethyl acetate. The organic layer was dried over NaA mixture of methyl gallate 9 (10 g, 53 mmol) and potassium carbonate (45 g, 320 mmol) in DMF (120 mL) was treated with benzyl bromide (210 mmol, 25.7 mL) and stirred at 40° C. under an argon atmosphere for 24 h. The reaction mixture was filtered and the filtrate evaporated to dryness. The residue was dissolved in minimum amount of methylene chloride and diluted with an equal volume of hexanes and loaded onto a short silica gel pad in a sintered glass funnel. The silica was eluted with hexanes (300 mL) to remove excess benzyl bromide and the eluant discarded. The product was then eluted with methylene chloride: hexanes (1:1, 300 mL) followed by methylene chloride (500 mL) and the eluants combined and evaporated to afford pure benzyl product 10 as an off-white solid (100percent yield). 1H NMR (300 MHz, CDCl3): δ 3.88 (s, 3H, CH3), 5.11 and 5.13 (2s, 6H, OCH2), 7.35-7.41 (m, 17H, Ar-H). [0119] To a solution of 3, 4, 5-tribenzyl-methyl gallate 10 (10 g, 22 mmol) in dry tetrahydrofuran (75 mL) was added solid lithium aluminum hydride (1.25 g, 33 mmol) in small portions. The suspension was heated to reflux under argon for 2 h. The reaction was cooled to 0° C. and carefully quenched with the dropwise addition of water. The slurry was then extracted with ethylacetate/hexanes. The organic solution was dried with saturated brine, followed by anhydrous magnesium sulfate, filtered and evaporated to afford the pure alcohol 11 as a white solid (8.9 g, 95percent yield). 1H NMR (300 MHz, CDCl3): δ 4.6 (d, 2H, CH2), 5.04 and 5.11 (2s, 6H, OCH2), 6.67 (s, 2H, 2, 6-Ar-H), 7.25-7.43 (m, 15H, Ar-H). [0120] To a solution of 3, 4, 5-tribenzyloxy-benzyl alcohol 11 (8.9 g, 21 mmol) in methylene chloride (200 mL) at 0° C. was added pyridinium chlorochromate (5.43 g, 25 mmol) in small portions with vigorous stirring. The cooling was discontinued and reaction stirred at room temperature for 4 h. The dark brown suspension was filtered over a long pad of silica gel in a sintered glass funnel, and eluted with methylene chloride, until all the pure product eluted out. The organic filtrate was evaporated down to give the pure product 12 as a soft white solid (8.1 g, 91.5percent yield). 1H NMR (300 MHz, CDCl3): δ 5.16 (s, 6H, OCH2), 7.18 (s, 2H, 2, 6-Ar-H), 7.26-7.41 (m, 15H, Ar-H), 9.80 (s, 1H, CHO).Methyl 3, 4, 5-Tribenzyloxybenzoate. Benzyl bromide (10.6 mL, 89.7 mmol) was added to a solution of methyl 3, 4, 5-trihydroxybenzoate (5.0 g, 27 mmol) and potassium carbonate (oven dried, 12.4 g, 89.7 mmol) in 250 mL of acetone. This solution was heated to reflux under Ar for 24 h. The reaction mixture was cooled, treated with triethylamine (7.6 mL, 54 mmol), and extracted with EtOAc. The organic layer washed sequentially with 10percent H3, 4, 5-trihydroxybenzoate (9.6 kg, 1.0 eq.) and DMF (76.8 liters) are charged to a reactor at 10-25° C. 2. To the reactor is charged KTo a stirred solution of methyl 3, 4, 5-trihydroxybenzoate 12 (0.94 g, 5.15 mmol) and potassium carbonate (6.56 g, 25.7 mmol)in DMF (20 mL), benzyl bromide (4.4 g, 25.7 mmol) was added. The reaction mixture was stirred at 60 °C under NCompound 2 (1 g, 5.43 mmol) was taken in dry DMF (60 mL) and was stirred in presence of K2CO3 (10 g , 54.34 mmol). Benzyl bromide (4 mL, 16.70 mmol) was added to the stirred solution and stirring was continued for 6h. The progress of reaction was monitored by TLC. After completion of reaction, the reaction mixture was extracted with EtOAc and washed with water. The organic layer was then dried over anhydrous Na2SO4, and the solvent was evaporated to get the crude product, which was purified by column chromatography using using 5percent EtOAc in petroleum ether as the eluent to get the pure product 3 as white powder (2.2 g, yield 89 percent). 1H NMR (CDCl3, 400 MHz): 7.37-7.35 (m, 4H), 7.33-7.24 (m, 10H), 7.20-7.17 (m, 3H), 5.06 (s, 4H), 5.04 (s, 2H), 3.82 (s, 3H); FTIR (KBr, cm-1 ): 3411, 3044, 3031, 2948, 2878, 1715, 1589, 1499, 1453, 1110 and 754 cm-1 ; mp. 94CGeneral procedure: Gallic acid (1.5 g, 8.83 mmol) was dissolved in 9 cm3 methanol, conc.0.45 cm3 sulfuric acid was added thereto, and the mixturewas stirred under reflux for 5 h. The reaction vessel wascooled down to room temperature and the reaction mixturewas neutralized with saturated sodium bicarbonate solutionat 0 C. Then, the organic solvent was removed at reducedpressure, and the residue dissolved in ethyl acetate, washedwith saturated sodium bicarbonate solution, dried overanhydrous sodium sulfate, and concentrated to give methyl1.39 g 3, 4, 5-trihydroxybenzoate (7.55 mmol, 86percent yield)as white solid. This compound was used in the next stepreaction without further purification.Gallic acid (1.5 g, 8.83 mmol) was dissolved in 9 cm3 methanol, conc.0.45 cm3 sulfuric acid was added thereto, and the mixturewas stirred under reflux for 5 h. The reaction vessel wascooled down to room temperature and the reaction mixturewas neutralized with saturated sodium bicarbonate solutionat 0 C. Then, the organic solvent was removed at reducedpressure, and the residue dissolved in ethyl acetate, washedwith saturated sodium bicarbonate solution, dried overanhydrous sodium sulfate, and concentrated to give methyl1.39 g 3, 4, 5-trihydroxybenzoate (7.55 mmol, 86percent yield)as white solid. This compound was used in the next stepreaction without further purification.A mixture of methyl 2.114 g 3, 4, 5-tris(benzyloxy)benzoate(4.66 mmol), sodium hydroxide (96 mmol), 6 cm3MeOH, and 12 cm3 dioxane was heated at reflux for 4 h.The solvent was removed and the resulting residue waspartitioned between water and ethyl acetate. The combinedorganic layers were washed with brine, dried (Na2SO4), and concentrated at reduced pressure to give the titlecompound (1.984 g, 4.51 mmol, 97percent yield) as a whitesolid. Spectral data were in accordance with those previouslyreportedMethyl 3, 4, 5-trihydroxybenzoate (16) (55.24 g, 0.3 mol), benzyl chloride (113.93 g, 0.9 mol), potassium carbonate (124.39 g, 0.9 mol) and potassium iodide (catalytic amount) were mechanically stirred in dry DMSO (200 mL) at room temperature overnight. Water (200 mL) was added and the crude product isolated by filtration. Evaporation of residual solvents in a vacuum desiccator left a pale yellow solid which was essentially pure product. Yield: 128.2 g (94percent).Preparation of (AB)Methyl 3, 4, 5-trihydroxybenzoate (16) (55.24 g

Intermediate in the production of Gallic Acid derivatives.

Molecular Weight:454.5
XLogP3:6.2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:11
Exact Mass:454.17802393
Monoisotopic Mass:454.17802393
Topological Polar Surface Area:54
Heavy Atom Count:34
Complexity:545
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes