2,3-dihydro-1,4-benzodioxine-6-carboxylicacidmethylester

A mixture of 3, 4-dihydroxybenzoic acid methyl ester (5.2 g, 31 mmol), 1, 2- dibromoethane (2.9 mL, 34 mmol), and pulverized KOH (3.8 g, 68 mmol) in MeOH was heated at reflux for 30 hrs. After removal of the solvent under reduced pressure, the residue was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water, dried over MgSO4, concentrated in vacuo and purified by purified by column chromatography on silica gel eluting with 40percent ethyl acetate in hexane to yield methyl 2, 3-dihydrobenzo[][l , 4]dioxine-6-carboxylate (780 mg, 13percent) along with the unreacted starting material (2.6 g). 1H NMR (DMSO-d6, 600 MHz) delta 7.45 (d, IH, J=8.4 Hz), 7.39 (s, IH), 6.96 (d, IH, J=8.4 Hz), 4.33-4.28 (m, 4H), 3.80 (s, 3H); MS (ES+) m/z 195.1 (M+H)+.Step A Preparation of 3, 4-ethylenedioxybenzoic acid methyl ester A solution of 4.20 g. of 3, 4-dihydroxybenzoic acid methyl ester in 10.0 ml. of methanol is combined with 7.0 g. of sodium methoxide and then 15.0 g. of 1, 2-dibromoethane is added. The resulting mixture is refluxed under nitrogen for 24 hours, then cooled, filtered, evaporated in vacuo and the resulting oil dissolved in 50 ml. of chloroform. The resulting solution after again filtering is chromatographed over 100 ml. of silica gel eluding with chloroform to obtain 3, 4-ethylenedioxybenzoic acid methyl ester, m.p. 43°-45°C.Step A: Preparation of 3, 4-ethylenedixoybenzoic acid methyl ester. A solution of 4.20 g. of 3, 4-dihydroxybenzoic acid methyl ester in 10.0 ml. of methanol is combined with 7.0 g. of sodium methoxide and then 15.0 g. of 1, 2-dibromoethane is added. The resulting mixture is refluxed under nitrogen for 24 hours, then cooled, filtered, evaporated in vacuo and the resulting oil dissolved in 50 ml. of chloroform. The resulting solution after again filtering is chromatographed over 100 ml. of silica gel eluding with chloroform to obtain 3, 4-ethylenedioxybenzoic acid methyl ester, m.p. 43°-45° C.In the three-necked flask under a nitrogen atmosphere, compound 2(1mmol) was dissolved in dry acetone (10 ml), and then added anhydrous potassium carbonate (2mmol). After that, the acetone solution containing dibromomethane (1mmol) was added dropwise then refluxed for 24 h. The reaction solution was evaporated reduced pressure distillation. The appropriate amount of water was added in the residue, and extracted with ethyl acetate (3×40 ml). Combined organic layer and dried with anhydrous magnesium sulfate. Then the solvent was removed by reduced pressure steam to give the crude product, the crude product is purified by column chromatography [eluent: V (petroleum ether): V (ethyl acetate) = 4: 1] to give white solid (compounds 3).In the three-necked flask under a nitrogen atmosphere, compound 2(1mmol) was dissolved in dry acetone (10mL), and then added anhydrous potassium carbonate (2mmol). After that, the acetone solution containing dibromomethane (1mmol) was added dropwise then refluxed for 24h. The reaction solution was evaporated reduced pressure distillation. The appropriate amount of water was added in the residue, and extracted with ethyl acetate (3×40mL). Combined organic layer and dried with anhydrous magnesium sulfate. Then the solvent was removed by reduced pressure steam to give the crude product, the crude product is purified by column chromatography [eluant: V (petroleum ether): V (ethyl acetate)=4: 1] to give white solid (compounds 3).(2) step (1) the obtained solid product, acetone, Dibromoethane, potassium carbonate reflux the reaction, the obtained solid product;Step (1) the obtained solid product, acetone, Dibromoethane, the consumption of potassium carbonate, the proportion of 1:20:1: 1.5, wherein step (1) the obtained solid product, Dibromoethane, potassium carbonate to meter mmol, in terms of ml of acetone, reflux the reaction time is 15h.Compound 1 (1 mmol) and potassium carbonate (0.28 g, 2 mmol) were dissolved in dry acetone (10 mL) and stirred for15 min at room temperature. Afterward, the mixture was slowlyheated while the 1, 2-dibromoethane (1 mmol) was dropwiseadded and then refluxed for 24 h. The reaction mixture was dilutedwith water and extracted with ethyl acetate. Combined organiclayer and dried with anhydrous sodium sulfate. The solvent wasevaporated under reduced pressure and the crude product waspurified by silica gel column chromatography (VDCM/VEtOAc = 4:1)to give compound 2.Protocatechuic acid (0.0973 mol, 15 g) was dissolved in methanol (100 ml) with stirring, catalyzed by concentrated sulfuric acid. The mixture was stirred for about 20 h at 63°C and evaporated. The concentratedsolution was poured into 200 ml of ethyl acetate and 100 ml of water and stilled. The ethyl acetate solvent was evaporated togive white powdered compound 1.Compound 1 (0.06 mol, 10.0824 g) and 1, 2-dibromoethane (0.12 mol, 10.45 ml) were dissolved in acetone (100 ml)with stirring, using K2CO3 (0.24 mol, 33.16 g) as the acid binding agent. The mixture was stirred for about 24 h at 56°C. Theinsoluble substance was removed by filtration; the solvent was evaporated to obtain yellow powdered compound 2.

Molecular Weight:194.18
XLogP3:0.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:194.05790880
Monoisotopic Mass:194.05790880
Topological Polar Surface Area:44.8
Heavy Atom Count:14
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes