(3-hydroxyphenyl) acetate

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

Procedure: A mixture of 2-chloromethyl quinolin (2.3 g, 13.3 mmol), 3-hydroxyphenyl acetate (2.2 g, 13.3 mmol), excess powdered potassium carbonate (10 g) and a catalytic amount of potassium iodide (0.1 g) in dry acetone (150 ml) was refluxed overnight (18 hr.). The reaction mixture was filtered, and the filtrate was concentrated, taken up in ethyl acetate, and the organic extract was washed with a 5% NaOH solution and brine. After drying over MgSO4, all volatiles were removed from the organic extract, and the crude oil was chromatographed on silica gel (20% ethylacetate in hexanes) to obtain the methyl ester of the desired product (3.0 g). The reaction mixture was filtered the filtrate was concentrated the organic extract was washed with a 5% NaOH solution and brine After drying over MgSO4 all volatiles were removed from the organic extract the crude oil was chromatographed on silica gel (20% ethylacetate in hexanes)

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

Procedure: Resorcinol monoacetate (6.10 g, 40 mmol) in DMF (10 mL) was added dropwise to the mixture of NaH (95%, 0.92 g, 40 mmol) in DMF (50 mL). The mixture was stirred at room temperature for 10 min. Benzyl bromide (6.85 g, 40 mmol) in DMF (10 mL) was then added dropwise, and the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched slowly with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The organic phase was washed with brine (2×50 mL) and dried over Na2SO4. The solvent was removed in vacuo and the residue purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a white solid (5.30 g, 55%). 1H-NMR (300 MHz, CDCl3) δ 2.28 (s, 3 H), 5.03 (s, 2 H), 6.72 (m, 2 H), 6.85 (dd, 1 H, J=1.2, 4.1 Hz), 7.27 (t, 1 H, J=7.9 Hz), and 7.41 (m, 5 H). the mixture was stirred at room temperature for 2 h The reaction mixture was quenched slowly with water (100 mL) extracted with ethyl acetate (3×100 mL) The organic phase was washed with brine (2×50 mL) dried over Na2SO4 The solvent was removed in vacuo the residue purified by flash column chromatography (1:1 hexane:methylene chloride)

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

Procedure: Lithium bis(trimethylsilyl)amide (73 ml, 73 ml, 1M solution in THF) was added dropwise to a solution of resorcinol monoacetate (10 g, 65.7 mmol) in THF (100 ml) at 78° C. under argon. The solution was stirred for 10 minutes and then triisopropylsilyl chloride (15.5 ml, 73 mmol) was added via syringe. After stirring at room temperature overnight, the mixture was partitioned between water and ethyl acetate. The organic layer was dried, filtered and evaporated under vacuum to yield 13 g of crude 3-[1,1-bis(Methylethyl)-2-methyl-1-silapropoxy]phenyl acetate which was used in the next step without further purification. NMR 1H Cl3CD δ: 7.19 (t, 1H, J=8 Hz), 6.75 (m, 1H), 6.68 (m, 1H), 6.63 (t, 1H, J=4 Hz), 2.29 (s, 3H), 1.25 (m, 3H), 1.11 (d, 18H, J=7.0 Hz). After stirring at room temperature overnight the mixture was partitioned between water and ethyl acetate The organic layer was dried filtered evaporated under vacuum

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

Procedure: Lithium bis(trimethylsilyl)amide (73 ml, 73 ml, 1M solution in THF) was added dropwise to a solution of resorcinol monoacetate (10 g, 65.7 mmol) in THF (100 ml) at 78° C. under argon. The solution was stirred for 10 minutes and then triisopropylsilyl chloride (15.5 ml, 73 mmol) was added via syringe. After stirring at room temperature overnight, the mixture was partitioned between water and ethyl acetate. The organic layer was dried, filtered and evaporated under vacuum to yield 13 g of crude 3-[1,1-bis(Methylethyl)-2-methyl-1-silapropoxy]phenyl acetate which was used in the next step without further purification. NMR 1H Cl3CD δ: 7.19 (t, 1H, J=8 Hz), 6.75 (m, 1H), 6.68 (m, 1H), 6.63 (t, 1H, J=4 Hz), 2.29 (s, 3H), 1.25 (m, 3H), 1.11 (d, 18H, J=7.0 Hz). After stirring at room temperature overnight the mixture was partitioned between water and ethyl acetate The organic layer was dried filtered evaporated under vacuum

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

Procedure: Resorcinol monoacetate (6.10 g, 40 mmol) in DMF (10 mL) was added dropwise to the mixture of NaH (95%, 0.92 g, 40 mmol) in DMF (50 mL). The mixture was stirred at room temperature for 10 min. Benzyl bromide (6.85 g, 40 mmol) in DMF (10 mL) was then added dropwise, and the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched slowly with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The organic phase was washed with brine (2×50 mL) and dried over Na2SO4. The solvent was removed in vacuo and the residue purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a white solid (5.30 g, 55%). the mixture was stirred at room temperature for 2 h The reaction mixture was quenched slowly with water (100 mL) extracted with ethyl acetate (3×100 mL) The organic phase was washed with brine (2×50 mL) dried over Na2SO4 The solvent was removed in vacuo the residue purified by flash column chromatography (1:1 hexane:methylene chloride)

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

Procedure: Acetic acid 3-hydroxy-phenyl ester (1 ml, 9 mmol) was mixed with cyclobutanol (0.58 g, 8 mmol), triphenylphosphine (2.1 g, 8 mmol) and diisopropyl azodicarboxylate (1.57 ml, 8 mmol) in tetrahydrofuran (20 ml) at 0° C. under a nitrogen atmosphere. The mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was concentrated in-vacuo the residue was purified by chromatography on silica gel using ethyl acetate in pentane as eluant (gradient from 0:100 to 15:85) to give acetic acid 3-cyclobutoxy-phenyl ester (340 mg). The reaction mixture was concentrated in-vacuo the residue was purified by chromatography on silica gel

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

Procedure: Acetic acid 3-hydroxy-phenyl ester (1 ml, 9 mmol) was mixed with cyclobutanol (0.58 g, 8 mmol), triphenylphosphine (2.1 g, 8 mmol) and diisopropyl azodicarboxylate (1.57 ml, 8 mmol) in tetrahydrofuran (20 ml) at 0° C. under a nitrogen atmosphere. The mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was concentrated in-vacuo the residue was purified by chromatography on silica gel using ethyl acetate in pentane as eluant (gradient from 0:100 to 15:85) to give acetic acid 3-cyclobutoxy-phenyl ester (340 mg). The reaction mixture was concentrated in-vacuo the residue was purified by chromatography on silica gel

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

Procedure: Resorcinol monoacetate (6.10 g, 40 mmol) in DMF (10 mL) was added dropwise to a mixture of NaH (95%, 0.92 g, 40 mmol) in DMF (50 mL). The reaction mixture was stirred at room temperature for 10 min. Benzyl bromide (6.85 g, 40 mmol) in DMF (10 mL) was added dropwise and stirring was continued at room temperature for 2 h. The reaction was quenched carefully with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The organic phase was washed with brine (2×50 mL), dried over Na2 SO4, and concentrated in vacuo. The residue was then purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a white solid (5.30 g, 55%). 1H-NMR (300 MHz, CDCl3) δ 2.28 (s, 3H), 5.03 (s, 2H), 6.72 (m, 2H), 6.85 (dd, 1H), 7.27 (t, 1H), 7.41 (m, 5H). stirring was continued at room temperature for 2 h The reaction was quenched carefully with water (100 mL) extracted with ethyl acetate (3×100 mL) The organic phase was washed with brine (2×50 mL) dried over Na2 SO4 concentrated in vacuo The residue was then purified by flash column chromatography (1:1 hexane:methylene chloride)

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

Procedure: Resorcinol monoacetate (6.10 g, 40 mmol) in DMF (10 mL) was added dropwise to a mixture of NaH (95%, 0.92 g, 40 mmol) in DMF (50 mL). The reaction mixture was stirred at room temperature for 10 min. Benzyl bromide (6.85 g, 40 mmol) in DMF (10 mL) was added dropwise and stirring was continued at room temperature for 2 h. The reaction was quenched carefully with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The organic phase was washed with brine (2×50 mL), dried over Na2 SO4, and concentrated in vacuo. The residue was then purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a white solid (5.30 g, 55%). 1H-NMR (300 MHz, CDCl3) δ 2.28 (s, 3H), 5.03 (s, 2H), 6.72 (m, 2H), 6.85 (dd, 1H), 7.27 (t, 1H), 7.41 (m, 5H). stirring was continued at room temperature for 2 h The reaction was quenched carefully with water (100 mL) extracted with ethyl acetate (3×100 mL) The organic phase was washed with brine (2×50 mL) dried over Na2 SO4 concentrated in vacuo The residue was then purified by flash column chromatography (1:1 hexane:methylene chloride)

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

Procedure: A mixture of 2-chloromethyl quinolin (2.3 g, 13.3 mmol), 3-hydroxyphenyl acetate (2.2 g, 13.3 mmol), excess powdered potassium carbonate (10 g) and a catalytic amount of potassium iodide (0.1 g) in dry acetone (150 ml) was refluxed overnight (18 hr.). The reaction mixture was filtered, and the filtrate was concentrated, taken up in ethyl acetate, and the organic extract was washed with a 5% NaOH solution and brine. After drying over MgSO4, all volatiles were removed from the organic extract, and the crude oil was chromatographed on silica gel (20% ethylacetate in hexanes) to obtain the methyl ester of the desired product (3.0 g). The reaction mixture was filtered the filtrate was concentrated the organic extract was washed with a 5% NaOH solution and brine After drying over MgSO4 all volatiles were removed from the organic extract the crude oil was chromatographed on silica gel (20% ethylacetate in hexanes)

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

Procedure: A mixture of 2-chloromethyl quinolin (2.3 g, 13.3 mmol), 3-hydroxyphenyl acetate (2.2 g, 13.3 mmol), excess powdered potassium carbonate (10 g) and a catalytic amount of potassium iodide (0.1 g) in dry acetone (150 ml) was refluxed overnight (18 hr.). The reaction mixture was filtered, and the filtrate was concentrated, taken up in ethyl acetate, and the organic extract was washed with a 5% NaOH solution and brine. After drying over MgSO4, all volatiles were removed from the organic extract, and the crude oil was chromatographed on silica gel (20% ethylacetate in hexanes) to obtain the methyl ester of the desired product (3.0 g). The reaction mixture was filtered the filtrate was concentrated the organic extract was washed with a 5% NaOH solution and brine After drying over MgSO4 all volatiles were removed from the organic extract the crude oil was chromatographed on silica gel (20% ethylacetate in hexanes)

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

Procedure: Resorcinol monoacetate (6.10 g, 40 mmol) in DMF (10 mL) was added dropwise to the mixture of NaH (95%, 0.92 g, 40 mmol) in DMF (50 mL). The mixture was stirred at room temperature for 10 min. Benzyl bromide (6.85 g, 40 mmol) in DMF (10 mL) was then added dropwise, and the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched slowly with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The organic phase was washed with brine (2×50 mL) and dried over Na2SO4. The solvent was removed in vacuo and the residue purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a white solid (5.30 g, 55%). 1H-NMR (300 MHz, CDCl3) δ 2.28 (s, 3 H), 5.03 (s, 2 H), 6.72 (m, 2 H), 6.85 (dd, 1 H, J=1.2, 4.1 Hz), 7.27 (t, 1 H, J=7.9 Hz), and 7.41 (m, 5 H). the mixture was stirred at room temperature for 2 h The reaction mixture was quenched slowly with water (100 mL) extracted with ethyl acetate (3×100 mL) The organic phase was washed with brine (2×50 mL) dried over Na2SO4 The solvent was removed in vacuo the residue purified by flash column chromatography (1:1 hexane:methylene chloride)