2-methoxybenzene-1,3-diol

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium carbonate (281 mg, 1.98 mmol) was added to pyrogallol (100 mg, 0.79 mmol) in N,N-dimethylformamide (3.0 mL) at room temperature. After five minutes, methyl iodide (130 μL, 1.98 mmol) was added and the resulting solution was heated to 50° C. for 48 hours. Upon cooling to room temperature, water (20 mL) was added and the solution was extracted with EtOAc (3×20 mL). Combined organic fractions were dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc) to afford 19 as a colorless amorphous solid (44.2 mg, 34%): 1H NMR (CDCl3, 400 MHz) δ 6.89 (td, J=8.0, 0.9 Hz, ′H), 6.53 (dd, J=8.2, 0.8 Hz, 2H), 5.83 (bs, 2H), 3.90 (s, 3H). Upon cooling to room temperature the solution was extracted with EtOAc (3×20 mL) Combined organic fractions were dried (Na2SO4) filtered concentrated The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc)

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

Procedure: To a stirring solution of benzene-1,2,3-triol (2 g, 15.87 mmol) in acetone was added potassium bicarbonate (1.9 g, 19.04 mmol) and methyl iodide (3.3 g, 23.8 mmol) and the resultant reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure. The residue was diluted with ether, solid separated out was filtered and the filtrate was concentrated under reduced pressure to afford the crude product. The crude product was purified by flash column chromatography (silica gel, 0-15% ethyl acetate in pet ether) to afford 2-Methoxybenzene-1,3-diol as a solid (600 mg, 27%). the resultant reaction mixture was heated to reflux for 16 h filtered through celite the filtrate was concentrated under reduced pressure The residue was diluted with ether, solid separated out was filtered the filtrate was concentrated under reduced pressure to afford the crude product The crude product was purified by flash column chromatography (silica gel, 0-15% ethyl acetate in pet ether)

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

Procedure: To a stirring solution of benzene-1,2,3-triol (2 g, 15.87 mmol) in acetone was added potassium bicarbonate (1.90 g, 19.04 mmol) and methyl iodide (3.38 g, 23.80 mmol) and the resultant reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to RT and filtered through celite bed. The filtrate was concentrated under reduced pressure, triturated with diethyl ether and the obtained solid was separated and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography (silica gel, 0-15% ethyl acetate in pet ether) afforded 2-Methoxybenzene-1,3-diol as a solid (600 mg, 27.2%). 4-Bromo-2-methoxybenzene-1,3-diol: To a stirring solution of 2-methoxybenzene-1,3-diol (3.0 g, 21.42 mmol) in tetrahydrofuran (30 mL) at −78° C. was added N-bromosuccinimide (4.57 g, 25.71 mmol) and the reaction mixture was stirred at −78° C. for 2 h. The reaction mixture was diluted with ice-cold water and extracted with ethyl acetate (3×). The combined ethyl acetate layers were washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The obtained residue has mixture of products (mono and dibromo) which was used as such for further reactions (4.2 g). the resultant reaction mixture was heated to reflux for 16 h filtered through celite bed The filtrate was concentrated under reduced pressure triturated with diethyl ether the obtained solid was separated the filtrate was concentrated under reduced pressure Purification of the residue by flash chromatography (silica gel, 0-15% ethyl acetate in pet ether)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium carbonate (281 mg, 1.98 mmol) was added to pyrogallol (100 mg, 0.79 mmol) in N,N-dimethylformamide (3.0 mL) at room temperature. After five minutes, methyl iodide (130 μL, 1.98 mmol) was added and the resulting solution was heated to 50° C. for 48 hours. Upon cooling to room temperature, water (20 mL) was added and the solution was extracted with EtOAc (3×20 mL). Combined organic fractions were dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc) to afford 19 as a colorless amorphous solid (44.2 mg, 34%): 1H NMR (CDCl3, 400 MHz) 6.89 (td, J=8.0, 0.9 Hz, H), 6.53 (dd, J=8.2, 0.8 Hz, 2H), 5.83 (bs, 2H), 3.90 (s, 3H). Upon cooling to room temperature the solution was extracted with EtOAc (3×20 mL) Combined organic fractions were dried (Na2SO4) filtered concentrated The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium carbonate (281 mg, 1.98 mmol) was added to pyrogallol (100 mg, 0.79 mmol) in N,N-dimethylformamide (3.0 mL) at room temperature. After 5 minutes, methyl iodide (130 μL, 1.98 mmol) was added and the resulting solution was heated to 50° C. for 48 hours. Upon cooling to room temperature, water (20 mL) was added and the solution was extracted with EtOAc (3×20 mL). Combined organic fractions were dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc) to afford 19 as a colorless amorphous solid (44.2 mg, 34%): 1H NMR (CDCl3, 400 MHz) 6.89 (td, J=8.0, 0.9 Hz, H), 6.53 (dd, J=8.2, 0.8 Hz, 2H), 5.83 (bs, 2H), 3.90 (s, 3H). Upon cooling to room temperature the solution was extracted with EtOAc (3×20 mL) Combined organic fractions were dried (Na2SO4) filtered concentrated The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc)