methyl 2-(4-sulfanylphenyl)acetate

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

Procedure: To an ambient temperature solution of 4-mercaptophenylacetic acid (5.0 g, 29.72 mmol) in MeOH (250 mL) is added sulfuric acid (1.25 mL). The reaction is stirred at room temperature overnight. The reaction mixture is concentrated and the residue is partitioned between Et2O and water. The aqueous layer is extracted with Et2O and the combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed eluting with 0% to 30% EtOAC/Hexane to yield the title compound (3.69 g, 68%). 1H NMR (400 MHz, CDCl3) δ 7.21 (d, 2H, J=7.9 Hz), 7.12 (d, 2H, J=8.4 Hz), 3.66 (s, 3H), 3.54 (s, 2H). The reaction mixture is concentrated the residue is partitioned between Et2O and water The aqueous layer is extracted with Et2O the combined organic layers are washed with brine dried (MgSO4) filtered concentrated chromatographed eluting with 0% to 30% EtOAC/Hexane

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid methyl ester (500 mg, 2.7 mmol) and chloromethyl methyl ether (331 mg, 4.1 mmol) in acetonitrile (3 mL) and pyridine (1 mL) was heated under reflux for 16 h. At this time, the reaction was concentrated in vacuo. The residue was re-dissolved in ethyl acetate (10 mL) and was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded (4-methoxymethylsulfanyl-phenyl)-acetic acid methyl ester (482 mg, 77.6%) as a clear oil: EI-HRMS m/e calcd for C11H14O3S (M+) 226.0664, found 226.0664. under reflux for 16 h At this time, the reaction was concentrated in vacuo The residue was re-dissolved in ethyl acetate (10 mL) was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid (1.00 g, 5.94 mmol) in methanol (10 mL) was treated with a catalytic amount of concentrated sulfuric acid (2 drops). The reaction was heated under reflux for 2 h. At this time, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in chloroform and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford (4-mercapto-phenyl)-acetic acid methyl ester (1.04 g, 96%) as a colorless oil: EI-HRMS m/e calcd for C9H10O2S (M+) 182.0402, found 182.0405. The reaction was heated under reflux for 2 h At this time, the reaction mixture was concentrated in vacuo The residue was re-dissolved in chloroform washed with a saturated aqueous sodium bicarbonate solution The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: Dissolve methyl 4-mercaptophenylacetate (16.4 g, 90.3 mmol) in acetone (300 mL). Add potassium carbonate (13.7 g, 99.3 mmol), potassium iodide (1.47 g, 9.03 mmol) and t-butylbromoacetate (16 mL, 99.3 mmol). Heat at reflux for 20 hours then remove 200 mL of acetone in vacuo. Dilute the residue with ethyl ether (500 mL), wash with water (2×300 mL) and brine (300 mL). Dry (MgSO4) and evaporate the solvent in vacuo. Purify by flash chromatography to give the title compound. Heat at reflux for 20 hours then remove 200 mL of acetone in vacuo Dilute the residue with ethyl ether (500 mL) wash with water (2×300 mL) and brine (300 mL) Dry (MgSO4) evaporate the solvent in vacuo Purify by flash chromatography

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

Procedure: Dissolve methyl 4-mercaptophenylacetate (16.4 g, 90.3 mmol) in acetone (300 mL). Add potassium carbonate (13.7 g, 99.3 mmol), potassium iodide (1.47 g, 9.03 mmol) and t-butylbromoacetate (16 mL, 99.3 mmol). Heat at reflux for 20 hours then remove 200 mL of acetone in vacuo. Dilute the residue with ethyl ether (500 mL), wash with water (2×300 mL) and brine (300 mL). Dry (MgSO4) and evaporate the solvent in vacuo. Purify by flash chromatography to give the title compound. Heat at reflux for 20 hours then remove 200 mL of acetone in vacuo Dilute the residue with ethyl ether (500 mL) wash with water (2×300 mL) and brine (300 mL) Dry (MgSO4) evaporate the solvent in vacuo Purify by flash chromatography

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid methyl ester (500 mg, 2.7 mmol) and chloromethyl methyl ether (331 mg, 4.1 mmol) in acetonitrile (3 mL) and pyridine (1 mL) was heated under reflux for 16 h. At this time, the reaction was concentrated in vacuo. The residue was re-dissolved in ethyl acetate (10 mL) and was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded (4-methoxymethylsulfanyl-phenyl)-acetic acid methyl ester (482 mg, 77.6%) as a clear oil: EI-HRMS m/e calcd for C11H14O3S (M+) 226.0664, found 226.0664. under reflux for 16 h At this time, the reaction was concentrated in vacuo The residue was re-dissolved in ethyl acetate (10 mL) was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid (1.00 g, 5.94 mmol) in methanol (10 mL) was treated with a catalytic amount of concentrated sulfuric acid (2 drops). The reaction was heated under reflux for 2 h. At this time, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in chloroform and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford (4-mercapto-phenyl)-acetic acid methyl ester (1.04 g, 96%) as a colorless oil: EI-HRMS m/e calcd for C9H10O2S (M+) 182.0402, found 182.0405. The reaction was heated under reflux for 2 h At this time, the reaction mixture was concentrated in vacuo The residue was re-dissolved in chloroform washed with a saturated aqueous sodium bicarbonate solution The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of 4-mercapto-phenyl acetic acid (30 g, 178.34 mmol) in methanol (60 ml) was added sulfuric acid (9.5 mL, 178.34 mmol) dropwise. Reaction mixture was then heated at 60° C. for 3 hr, concentrated to remove methanol. The residue was neutralized with satd. aq. NaHCO3 solution and extracted with ethyl acetate (3×30 mL) washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified using column chromatography in 1% ethyl acetatae:hexane as eluent which afforded (4-mercapto-phenyl)-acetic acid methyl ester (27 g). Reaction mixture concentrated to remove methanol aq. NaHCO3 solution and extracted with ethyl acetate (3×30 mL) washed with brine dried over anhydrous sodium sulfate filtered concentrated Product was purified

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

Procedure: To an ambient temperature solution of 4-mercaptophenylacetic acid (5.0 g, 29.72 mmol) in MeOH (250 mL) is added sulfuric acid (1.25 mL). The reaction is stirred at room temperature overnight. The reaction mixture is concentrated and the residue is partitioned between Et2O and water. The aqueous layer is extracted with Et2O and the combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed eluting with 0% to 30% EtOAC/Hexane to yield the title compound (3.69 g, 68%). 1H NMR (400 MHz, CDCl3) δ 7.21 (d, 2H, J=7.9 Hz), 7.12 (d, 2H, J=8.4 Hz), 3.66 (s, 3H), 3.54 (s, 2H). The reaction mixture is concentrated the residue is partitioned between Et2O and water The aqueous layer is extracted with Et2O the combined organic layers are washed with brine dried (MgSO4) filtered concentrated chromatographed eluting with 0% to 30% EtOAC/Hexane

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid methyl ester (500 mg, 2.7 mmol) and chloromethyl methyl ether (331 mg, 4.1 mmol) in acetonitrile (3 mL) and pyridine (1 mL) was heated under reflux for 16 h. At this time, the reaction was concentrated in vacuo. The residue was re-dissolved in ethyl acetate (10 mL) and was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded (4-methoxymethylsulfanyl-phenyl)-acetic acid methyl ester (482 mg, 77.6%) as a clear oil: EI-HRMS m/e calcd for C11H14O3S (M+) 226.0664, found 226.0664. under reflux for 16 h At this time, the reaction was concentrated in vacuo The residue was re-dissolved in ethyl acetate (10 mL) was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid methyl ester (500 mg, 2.7 mmol) and chloromethyl methyl ether (331 mg, 4.1 mmol) in acetonitrile (3 mL) and pyridine (1 mL) was heated under reflux for 16 h. At this time, the reaction was concentrated in vacuo. The residue was re-dissolved in ethyl acetate (10 mL) and was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded (4-methoxymethylsulfanyl-phenyl)-acetic acid methyl ester (482 mg, 77.6%) as a clear oil: EI-HRMS m/e calcd for C11H14O3S (M+) 226.0664, found 226.0664. under reflux for 16 h At this time, the reaction was concentrated in vacuo The residue was re-dissolved in ethyl acetate (10 mL) was washed with a 1N aqueous hydrochloric acid solution (2×25 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: A solution of (4-mercapto-phenyl)-acetic acid (1.00 g, 5.94 mmol) in methanol (10 mL) was treated with a catalytic amount of concentrated sulfuric acid (2 drops). The reaction was heated under reflux for 2 h. At this time, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in chloroform and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford (4-mercapto-phenyl)-acetic acid methyl ester (1.04 g, 96%) as a colorless oil: EI-HRMS m/e calcd for C9H10O2S (M+) 182.0402, found 182.0405. The reaction was heated under reflux for 2 h At this time, the reaction mixture was concentrated in vacuo The residue was re-dissolved in chloroform washed with a saturated aqueous sodium bicarbonate solution The organic layer was dried over magnesium sulfate filtered concentrated in vacuo