methyl 2-(3,5-dihydroxyphenyl)acetate

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: A mixture of (3,5-dihydroxy-phenyl)-acetic acid methyl ester (from Aldrich, 70 g, 0.385 mole), benzylbromide (137 mL, 1.16 mole), potassium carbonate (160 g, 1.16 mole) and DMF (1.5 L) under N2 was mechanically stirred at room temperature overnight. The resulting reaction mixture was poured into a mixture of 1.5 L of ice-water with stirring. The precipitate was obtained by filtration and washed with heptane successively to remove benzyl bromide to give the title compounds (123.7 g) as a brown solid which was air dried for the next reaction. The resulting reaction mixture with stirring The precipitate was obtained by filtration washed with heptane successively to remove benzyl bromide

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trifluoromethanesulphonic anhydride (7.05 g, 25.0 mmol) was added dropwise to a solution of 3,5-dihydroxyphenyl acetic acid methyl ester (1.80 g, 10.0 mmol) and pyridine (4.9 mL, 60.0 mmol) in DCM (20 mL) at 0° C. The temperature was maintained at 0° C. for 15 mins before warming to room temperature and the mixture stirred for 18 hrs. The reaction was diluted with DCM washed with H2O, Na2CO3, dil. HCl, brine, dried (MgSO4) and evaporated under reduced pressure to give a yellow oil. The residue was purified by flash column chromatography (EtOAc:petroleum ether), yield 4.0 g (89%), 1H NMR (CDCl3) δ 7.31 (d, 2H), 7.17 (t, 1H), 3.74 (s, 3H), 7.73 (s, 2H). before warming to room temperature washed with H2O, Na2CO3, dil. HCl, brine dried (MgSO4) evaporated under reduced pressure to give a yellow oil The residue was purified by flash column chromatography (EtOAc:petroleum ether), yield 4.0 g (89%), 1H NMR (CDCl3) δ 7.31 (d, 2H), 7.17 (t, 1H), 3.74 (s, 3H), 7.73 (s, 2H)

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

Procedure: A mixture of (3,5-dihydroxy-phenyl)-acetic acid methyl ester (from Aldrich, 70 g, 0.385 mol), benzylbromide (137 mL, 1.16 mol), potassium carbonate (160 g, 1.16 mol) and DMF (1.5 L) under N2 was mechanically stirred at room temperature overnight. The resulting reaction mixture was poured into a mixture of 1.5 L of ice-water with stirring. The precipitate was obtained by filtration and washed with heptane successively to remove benzyl bromide to give the title compounds (123.7 g) as a brown solid which was air dried for the next reaction. 1H-NMR(CDCl3): δ 3.60 (s, 2H), 3.71(s,3H), 5.05 (s, 4H), 6.60 (s, 3H), 7.35-7.50 (m, 10H); Calcd for C23H22O4 (M+H) 363.15, Found 363. The resulting reaction mixture with stirring The precipitate was obtained by filtration washed with heptane successively to remove benzyl bromide

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

Procedure: A mixture of (3,5-dihydroxy-phenyl)-acetic acid methyl ester (from Aldrich, 70 g, 0.385 mol), benzylbromide (137 mL, 1.16 mol), potassium carbonate (160 g, 1.16 mol) and DMF (1.5 L) under N2 was mechanically stirred at room temperature overnight. The resulting reaction mixture was poured into a mixture of 1.5 L of ice-water with stirring. The precipitate was obtained by filtration and washed with heptane successively to remove benzyl bromide to give the title compounds (123.7 g) as a brown solid which was air dried for the next reaction. 1H-NMR (CDCl3): δ 3.60 (s, 2H), 3.71 (s, 3H), 5.05 (s, 4H), 6.60 (s, 3H), 7.35-7.50 (m, 10H); Calcd for C23H22O4 (M+H) 363.15. Found 363. The resulting reaction mixture with stirring The precipitate was obtained by filtration washed with heptane successively to remove benzyl bromide

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

Procedure: A mixture of (3,5-dihydroxy-phenyl)-acetic acid methyl ester (from Aldrich, 70 g, 0.385 mole), benzylbromide (137 mL, 1.16 mole), potassium carbonate (160 g, 1.16 mole) and DMF (1.5 L) under N2 was mechanically stirred at room temperature overnight. The resulting reaction mixture was poured into a mixture of 1.5 L of ice-water with stirring. The precipitate was obtained by filtration and washed with heptane successively to remove benzyl bromide to give the title compounds (123.7 g) as a brown solid which was air dried for the next reaction. 1H-NMR(CDCl3): δ 3.60 (s, 2H), 3.71(s,3H), 5.05 (s, 4H), 6.60 (s, 3H), 7.35-7.50 (m, 10H); Calcd for C23H22O4 (M+H) 363.15, Found 363. The resulting reaction mixture with stirring The precipitate was obtained by filtration washed with heptane successively to remove benzyl bromide

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

Procedure: A mixture of (3,5-dihydroxy-phenyl)-acetic acid methyl ester (from Aldrich, 70 g, 0.385 mol), benzylbromide (137 mL, 1.16 mol), potassium carbonate (160 g, 1.16 mol) and DMF (1.5 L) under N2 was mechanically stirred at room temperature overnight. The resulting reaction mixture was poured into a mixture of 1.5 L of ice-water with stirring. The precipitate was obtained by filtration and washed with heptane successively to remove benzyl bromide to give the title compounds (123.7 g) as a brown solid which was air dried for the next reaction. 1H-NMR(CDCl3): δ 3.60 (s, 2H), 3.71(s,3H), 5.05 (s, 4H), 6.60 (s, 3H), 7.35-7.50 (m, 10H); Calcd for C23H22O4 (M+H) 363.15, Found 363. The resulting reaction mixture with stirring The precipitate was obtained by filtration washed with heptane successively to remove benzyl bromide

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

Procedure: A mixture of (3,5-dihydroxy-phenyl)-acetic acid methyl ester (from Aldrich, 70 g, 0.385 mol), benzylbromide (137 mL, 1.16 mol), potassium carbonate (160 g, 1.16 mol) and DMF (1.5 L) under N2 was mechanically stirred at room temperature overnight. The resulting reaction mixture was poured into a mixture of 1.5 L of ice-water with stirring. The precipitate was obtained by filtration and washed with heptane successively to remove benzyl bromide to give the title compounds (123.7 g) as a brown solid which was air dried for the next reaction. 1H-NMR(CDCl3): δ 3.60 (s, 2H), 3.71(s,3H), 5.05 (s, 4H), 6.60 (s, 3H), 7.35-7.50 (m, 10H); Calcd for C23H22O4 (M+H) 363.15, Found 363. The resulting reaction mixture with stirring The precipitate was obtained by filtration washed with heptane successively to remove benzyl bromide

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

Procedure: Imidazole (230 mg, 3.38 mmol) was added to a solution of 3,5-dihydroxyphenylacetic acid methyl ester (530 mg, 2.91 mmol) in tetrahydrofuran (6.7 mL)-dichloromethane (6.7 mL) at room temperature. t-Butylchlorodiphenylsilane (0.75 mL, 2.9 mmol) was added under cooling with ice. Then, the ice bath was removed, and the mixture was stirred at room temperature for three hours. The reaction mixture was diluted with diethyl ether. 50% saturated aqueous ammonium chloride was added, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=3/1) to give the title compound (470 mg, 33%). under cooling with ice Then, the ice bath was removed The reaction mixture was diluted with diethyl ether 50% saturated aqueous ammonium chloride was added followed by extraction with diethyl ether The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography (hexane/ethyl acetate=3/1)

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

Procedure: Imidazole (230 mg, 3.38 mmol) was added to a solution of 3,5-dihydroxyphenylacetic acid methyl ester (530 mg, 2.91 mmol) in tetrahydrofuran (6.7 mL)-dichloromethane (6.7 mL) at room temperature. t-Butylchlorodiphenylsilane (0.75 mL, 2.9 mmol) was added under cooling with ice. Then, the ice bath was removed, and the mixture was stirred at room temperature for three hours. The reaction mixture was diluted with diethyl ether. 50% saturated aqueous ammonium chloride was added, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=3/1) to give the title compound (470 mg, 33%). under cooling with ice Then, the ice bath was removed The reaction mixture was diluted with diethyl ether 50% saturated aqueous ammonium chloride was added followed by extraction with diethyl ether The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography (hexane/ethyl acetate=3/1)

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

Procedure: A solution of methyl [3,5-dihydroxyphenyl]acetate (2.1 g, 11.5 mmol) in acetone (100 mL) was treated with potassium carbonate (2.4 g, 17.4 mmol), potassium iodide (0.38 g, 2.31 mmol) and benzyl bromide (1.5 mL, 12.7 mmol), and the mixture was stirred at room temperature overnight. The reaction was diluted with water, and was extracted with dichloromethane (×3). Combined organic extracts were dried over sodium sulfate and evaporated in vacuo. The crude material was purified on a Biotage™ 40 M column (silica), eluting with 40% ethyl acetate/hexane, to give methyl [3-benzyloxy-5-hydroxyphenyl]acetate (1.0 g, 33%). 1H NMR (400 MHz, CDCl3): δ 7.32-7.42 (m, 5H), 6.48 (d, J=1.4 Hz, 1H), 6.38-6.39 (m, 2H), 4.99 (s, 2H), 3.69 (s, 3H), 3.53 (s, 2H). was extracted with dichloromethane (×3) Combined organic extracts were dried over sodium sulfate evaporated in vacuo The crude material was purified on a Biotage™ 40 M column (silica) eluting with 40% ethyl acetate/hexane