methyl 2,3-dihydroxybenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In one embodiment, the compounds can be prepared as shown in Scheme II. A dihydroxy benzoic acid methyl ester is reacted with benzyl chloride, to produce a Bis-benzyloxy benzoic acid methyl ester (1). The Bis-benzyloxy benzoic acid methyl ester can then be heated with LiOH to give a Bis-benzyloxy benzoic acid (2). The Bis-benzyloxy benzoic acid (2) is then reacted with an aminophenyl to produce a phenyl-benzamide (3). The phenyl-benzamide (3) is then reacted with hydrazine to give a triazol (4). The hydroxy groups can then be unprotected in the presence of palladium on charcoal to give the final product. In one embodiment, the compounds can be prepared

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In one embodiment, the compounds can be prepared as shown in Scheme II. A dihydroxy benzoic acid methyl ester is reacted with benzyl chloride, to produce a Bis-benzyloxy benzoic acid methyl ester (1). The Bis-benzyloxy benzoic acid methyl ester can then be heated with LiOH to give a Bis-benzyloxy benzoic acid (2). The Bis-benzyloxy benzoic acid (2) is then reacted with an aminophenyl to produce a phenyl-benzamide (3). The phenyl-benzamide (3) is then reacted with hydrazine to give a triazol (4). The hydroxy groups can then be unprotected in the presence of palladium on charcoal to give the final product. In one embodiment, the compounds can be prepared

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dihydroxybenzoic acid (5 g), methanol (50 ml) and concentrated sulphuric acid (10 drops) was stirred and heated to 60° C. for 24 hours. The mixture was evaporated and the residue was taken up in ethyl acetate. The organic solution was washed with a saturated solution of sodium bicarbonate, dried over magnesium sulphate and evaporated to give methyl 2,3-dihydroxybenzoate (2.19 g); NMR Spectrum: (CDCl3) 3.95 (s, 3H), 5.7 (s, 1H), 6.8 (t, 1H), 7.15 (d, H), 7.35 (d, H). The mixture was evaporated The organic solution was washed with a saturated solution of sodium bicarbonate dried over magnesium sulphate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 2,3-dihydroxybenzoate (27 g, 160 mmol) in dichloromethane (300 mL) was cooled to 0° C. and powdered potassium carbonate (23.3 g, 169 mmol) was added. The reaction mixture was then added benzoyl chloride (19.6 mL, 169 mmol) and the mixture was allowed to warm to room temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo and the residue was partitioned with ethyl acetate and 0.3M aqueous hydrochloric acid. The organic layer was washed with brine, dried over anhydrous magnesium sulfate. Filtration and concentration afforded 42.1 g (97%) of crude methyl 2-hydroxy-3-[(phenylcarbonyl)oxy]benzoate as an orange oil: 1H NMR (400 MHz, d4-MeOH): 8.17 (dd, J=1.6, 12.5 Hz, 2H), 7.80 (dd, J=1.6, 8.0 Hz, 1H), 7.71-7.67 (m, 1H), 7.57-7.53 (m, 2H), 7.41 (dd, J=1.8, 8.0 Hz, 1H), 6.97 (t, J=8.6 Hz, 1H), 3.96 (s, 3H). The reaction mixture was concentrated in vacuo the residue was partitioned with ethyl acetate and 0.3M aqueous hydrochloric acid The organic layer was washed with brine dried over anhydrous magnesium sulfate Filtration and concentration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 2,3-dihydroxybenzoate (27 g, 160 mmol) in dichloromethane (300 mL) was cooled to 0° C. and powdered potassium carbonate (23.3 g, 169 mmol) was added. The reaction mixture was then added benzoyl chloride (19.6 mL, 169 mmol) and the mixture was allowed to warm to room temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo and the residue was partitioned with ethyl acetate and 0.3M aqueous hydrochloric acid. The organic layer was washed with brine, dried over anhydrous magnesium sulfate. Filtration and concentration afforded 42.1 g (97%) of crude methyl 2-hydroxy-3-[(phenylcarbonyl)oxy]benzoate as an orange oil: 1H NMR (400 MHz, d4-MeOH): 8.17 (dd, J=1.6, 12.5 Hz, 2H), 7.80 (dd, J=1.6, 8.0 Hz, 1H), 7.71-7.67 (m, 1H), 7.57-7.53 (m, 2H), 7.41 (dd, J=1.8, 8.0 Hz, 1H), 6.97 (t, J=8.6 Hz, 1H), 3.96 (s, 3H). The reaction mixture was concentrated in vacuo the residue was partitioned with ethyl acetate and 0.3M aqueous hydrochloric acid The organic layer was washed with brine dried over anhydrous magnesium sulfate Filtration and concentration

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2,3-dihydroxybenzoate (2.18 g, 12.97 mmol), 2-bromoethyl methyl ether (4.50 g, 32.42 mmol), and potassium carbonate (6.91 g, 50.0 mmol) in DMF (20 mL) was stirred at 60° C. for 16 h. The reaction mixture was diluted with ethyl acetate (300 mL), washed with 5% aqueous LiCl (2×50 mL), and brine (50 mL), dried with sodium sulfate, and concentrated to provide crude methyl 2,3-bis{[2-(methyloxy)ethyl]oxy}benzoate (3.49 g, 95% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ7.32 (dd, 1H), 7.05 (m, 2H), 4.22 (m, 2H), 4.15 (m, 2H), 3.88 (s, 3H), 3.75 (m, 4H), 3.43 (s, 6H). washed with 5% aqueous LiCl (2×50 mL), and brine (50 mL) dried with sodium sulfate concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2,3-dihydroxybenzoate (2.18 g, 12.97 mmol), 2-bromoethyl methyl ether (4.50 g, 32.42 mmol), and potassium carbonate (6.91 g, 50.0 mmol) in DMF (20 mL) was stirred at 60° C. for 16 h. The reaction mixture was diluted with ethyl acetate (300 mL), washed with 5% aqueous LiCl (2×50 mL), and brine (50 mL), dried with sodium sulfate, and concentrated to provide crude methyl 2,3-bis{[2-(methyloxy)ethyl]oxy}benzoate (3.49 g, 95% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ7.32 (dd, 1H), 7.05 (m, 2H), 4.22 (m, 2H), 4.15 (m, 2H), 3.88 (s, 3H), 3.75 (m, 4H), 3.43 (s, 6H). washed with 5% aqueous LiCl (2×50 mL), and brine (50 mL) dried with sodium sulfate concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,3-dihydroxybenzoic acid (33.0 g, 214 mmol) in methanol (200 mL) was added sulfuric acid (5.0 mL) and the mixture was refluxed for 14 hours. The solvent was then distilled off under reduced pressure. To that residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide 35.0 g of methyl 2,3-dihydroxybenzoate. A mixture of this compound (35.0 g, 208 mmol), ethyl bromoacetate (70.0 g, 420 mmol), and potassium carbonate (58.0 g, 420 mmol) in acetone (400 mL) was stirred for 14 hours, and filtered. The filtrate was concentrated under reduced pressure to provide 58.0 g of the title compound. Yield 80%. Oil. the mixture was refluxed for 14 hours The solvent was then distilled off under reduced pressure To that residue was added water the mixture was extracted with ethyl acetate The organic layer was washed with water dried over MgSO4 filtered The filtrate was concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to the method of (Example 99) <Step 1>, from methyl 2,3-dihydroxybenzoate (1 g) and m-tolyl boronic acid (0.97 g) that are commercially available, the subject compound (0.56 g) was obtained as pale yellow oil.