2-[2-(2-hydroxyethyl)phenyl]ethanol

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

Procedure: 2-[2-(2-Hydroxy-ethyl)-phenyl]-ethanol (6.77 g/40 mmol) was dissolved in methylene chloride (100 mL) and cooled to 0° C. Triethylamine (11.0 mL/80 mmol) and methanesulfonyl chloride (5.25 mL/65 mmol) were added sequentially via addition funnel (dropwise). After an hour the reaction was poured into a separatory funnel and sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL). The resulting organic solution was dried over magnesium sulfate, filtered and concentrated. Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride afforded methanesulfonic acid 2-[2-(2-hydroxy-ethyl)-phenyl]-ethyl ester (2.25 g/23%). 1H NMR (400 MHz, CDCl3) δ 7.25 (m, 4H), 4.42 (t, J=7.1 Hz, 2H), 3.88 (m, 2H), 3.15 (t, J=7.1 Hz, 2H), 2.93 (t, J=7.1 Hz, 2H), 2.85 (s, 3H). After an hour the reaction was poured into a separatory funnel sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL) The resulting organic solution was dried over magnesium sulfate filtered concentrated Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride

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

Procedure: 2-[2-(2-Hydroxy-ethyl)-phenyl]-ethanol (6.77 g/40 mmol) was dissolved in methylene chloride (100 mL) and cooled to 0° C. Triethylamine (11.0 mL/80 mmol) and methanesulfonyl chloride (5.25 mL/65 mmol) were added sequentially via addition funnel (dropwise). After an hour the reaction was poured into a separatory funnel and sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL). The resulting organic solution was dried over magnesium sulfate, filtered and concentrated. Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride afforded methanesulfonic acid 2-[2-(2-hydroxy-ethyl)-phenyl]-ethyl ester (2.25 g/23%). 1H NMR (400 MHz, CDCl3) δ 7.25 (m, 4H), 4.42 (t, J=7.1 Hz, 2H), 3.88 (m, 2H), 3.15 (t, J=7.1 Hz, 2H), 2.93 (t, J=7.1 Hz, 2H), 2.85 (s, 3H). After an hour the reaction was poured into a separatory funnel sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL) The resulting organic solution was dried over magnesium sulfate filtered concentrated Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride

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

Procedure: (2-Carboxymethyl-phenyl)-acetic acid (5.0 g/25 mmol) was dissolved in THF (100 mL) and cooled to 0° C. Borane (1 M in THF, 100 mL/100 mmol) was then added dropwise while stirring (hydrogen evolution). The reaction was left to stir a 0° C. for four hours then carefully quenched by the addition of water (ca. 20 mL). The reaction was partitioned between diethyl ether (200 mL) and water (200 mL). The organic layer was extracted with an additional portion of ether (100 mL) and the combined organics washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated. To give 2-[2-(2-Hydroxy-ethyl)-phenyl]-ethanol (3.3 g/80%). 1H NMR (400 MHz, CDCl3) δ 7.2 (m, 4H), 3.9 (t, J=6.8 Hz, 4H), 2.95 (t, J=6.8 Hz, 4H). The reaction was left then carefully quenched by the addition of water (ca. 20 mL) The reaction was partitioned between diethyl ether (200 mL) and water (200 mL) The organic layer was extracted with an additional portion of ether (100 mL) the combined organics washed with brine (100 mL) dried over magnesium sulfate filtered concentrated

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

Procedure: Lithium aluminum hydride (0.332 mol) and tetrahydrofuran (THF, 175 mL) are placed in a dry 500-mL three-necked round-bottom flask fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer. The mixture is cooled with an ice bath and 1,2-phenylene diacetic acid (0.165 mol) in THF (100 mL) is added dropwise to the stirring mixture. After the addition is complete, the flask is removed from the ice bath and allowed to warm to room temperature. The reaction mixture is heated at reflux for two hours, then stirred overnight at room temperature. After cooling the mixture with an ice bath, water (12.6 mL) is added dropwise, followed by the successive dropwise addition of 15 percent aqueous sodium hydroxide (12.6 mL) and water (38 mL). The resulting mixture is warmed to room temperature, and the solids separated by vacuum filtration. The filtrate is placed on a rotary evaporator to remove the solvent. The remaining solid is recrystallized from toluene-hexane to give the 1,2-di(hydroxyethyl)benzene. fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer The mixture is cooled with an ice bath After the addition the flask is removed from the ice bath The reaction mixture is heated at reflux for two hours After cooling the mixture with an ice bath water (12.6 mL) is added dropwise followed by the successive dropwise addition of 15 percent aqueous sodium hydroxide (12.6 mL) and water (38 mL) The resulting mixture is warmed to room temperature the solids separated by vacuum filtration The filtrate is placed on a rotary evaporator to remove the solvent The remaining solid is recrystallized from toluene-hexane

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

Procedure: Lithium aluminum hydride (0.332 mol) and tetrahydrofuran (THF, 175 mL) are placed in a dry 500-mL three-necked round-bottom flask fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer. The mixture is cooled with an ice bath and 1,2-phenylene diacetic acid (0.165 mol) in THF (100 mL) is added dropwise to the stirring mixture. After the addition is complete, the flask is removed from the ice bath and allowed to warm to room temperature. The reaction mixture is heated at reflux for two hours, then stirred overnight at room temperature. After cooling the mixture with an ice bath, water (12.6 mL) is added dropwise, followed by the successive dropwise addition of 15 percent aqueous sodium hydroxide (12.6 mL) and water (38 mL). The resulting mixture is warmed to room temperature, and the solids separated by vacuum filtration. The filtrate is placed on a rotary evaporator to remove the solvent. The remaining solid is recrystallized from toluene-hexane to give the 1,2-di(hydroxyethyl)benzene. fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer The mixture is cooled with an ice bath After the addition the flask is removed from the ice bath The reaction mixture is heated at reflux for two hours After cooling the mixture with an ice bath water (12.6 mL) is added dropwise followed by the successive dropwise addition of 15 percent aqueous sodium hydroxide (12.6 mL) and water (38 mL) The resulting mixture is warmed to room temperature the solids separated by vacuum filtration The filtrate is placed on a rotary evaporator to remove the solvent The remaining solid is recrystallized from toluene-hexane

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

Procedure: Lithium aluminum hydride (0.332 mol) and tetrahydrofuran (THF, 175 mL) are placed in a dry 500-mL three-necked round-bottom flask fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer. The mixture is cooled with an ice bath and 1.2-phenylene diacetic acid (0.165 mol) in THF (100 mL) is added dropwise to the stirring mixture. After the addition is complete, the flask is removed from the ice bath and allowed to warm to room temperature. The reaction mixture is heated at reflux for two hours, then stirred overnight at room temperature. After cooling the mixture with an ice bath, water (12.6 mL) is added dropwise, followed by the successive dropwise addition of 15 percent aqueous sodium hydroxide (12.6 mL) and water (38 mL). The resulting mixture is warmed to room temperature, and the solids separated by vacuum filtration. The filtrate is placed on a rotary evaporator to remove the solvent. The remaining solid is recrystallized from toluene-hexane to give the 1,2-di(hydroxyethyl)benzene. fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer The mixture is cooled with an ice bath After the addition the flask is removed from the ice bath The reaction mixture is heated at reflux for two hours After cooling the mixture with an ice bath water (12.6 mL) is added dropwise followed by the successive dropwise addition of 15 percent aqueous sodium hydroxide (12.6 mL) and water (38 mL) The resulting mixture is warmed to room temperature the solids separated by vacuum filtration The filtrate is placed on a rotary evaporator to remove the solvent The remaining solid is recrystallized from toluene-hexane

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

Procedure: To a solution of 2,2′-(1,2-phenylene)diacetic acid (10 g, 51.5 mmol) in THF (100 mL) was added to LAH in THF (90 mL) dropwise, the mixture was refluxed for 18 hours. The mixture was cooled in ice bath and carefully added water (8 mL) dropwise, followed by 1 N NaOH (8 mL), then removed the ice bath added water slowly with stirring until the gray precipitate turns white. The mixture was filtrated and the filtrate was concentrated to give crude 2,2′-(1,2-phenylene)diethanol (8 g, 94%). 1H-NMR (CDCl3): 2.02 (s, 3H), 2.97 (m, 4H), 3.83 (m, 2H), 4.12 (m, 1H), 4.24 (t, 1H), 7.19 (m, 4H). the mixture was refluxed for 18 hours The mixture was cooled in ice bath removed the ice bath added water slowly The mixture was filtrated the filtrate was concentrated

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

Procedure: To a solution of 2,2′-(1,2-phenylene)diacetic acid (10 g, 51.5 mmol) in THF (100 mL) was added to LAH in THF (90 mL) dropwise, the mixture was refluxed for 18 hours. The mixture was cooled in ice bath and carefully added water (8 mL) dropwise, followed by 1 N NaOH (8 mL), then removed the ice bath added water slowly with stirring until the gray precipitate turns white. The mixture was filtrated and the filtrate was concentrated to give crude 2,2′-(1,2-phenylene)diethanol (8 g, 94%). 1H-NMR (CDCl3): 2.02 (s, 3H), 2.97 (m, 4H), 3.83 (m, 2H), 4.12 (m, 1H), 4.24 (t, 1H), 7.19 (m, 4H). the mixture was refluxed for 18 hours The mixture was cooled in ice bath removed the ice bath added water slowly The mixture was filtrated the filtrate was concentrated

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

Procedure: 2-[2-(2-Hydroxy-ethyl)-phenyl]-ethanol (6.77 g/40 mmol) was dissolved in methylene chloride (100 mL) and cooled to 0° C. Triethylamine (11.0 mL/80 mmol) and methanesulfonyl chloride (5.25 mL/65 mmol) were added sequentially via addition funnel (dropwise). After an hour the reaction was poured into a separatory funnel and sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL). The resulting organic solution was dried over magnesium sulfate, filtered and concentrated. Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride afforded methanesulfonic acid 2-[2-(2-hydroxy-ethyl)-phenyl]-ethyl ester (2.25 g/23%). 1H NMR (400 MHz, CDCl3) δ 7.25 (m, 4H), 4.42 (t, J=7.1 Hz, 2H), 3.88 (m, 2H), 3.15 (t, J=7.1 Hz, 2H), 2.93 (t, J=7.1 Hz, 2H), 2.85 (s, 3H). After an hour the reaction was poured into a separatory funnel sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL) The resulting organic solution was dried over magnesium sulfate filtered concentrated Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride

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

Procedure: (2-Carboxymethyl-phenyl)-acetic acid (5.0 g/25 mmol) was dissolved in THF (100 mL) and cooled to 0° C. Borane (1 M in THF, 100 mL/100 mmol) was then added dropwise while stirring (hydrogen evolution). The reaction was left to stir a 0° C. for four hours then carefully quenched by the addition of water (ca. 20 mL). The reaction was partitioned between diethyl ether (200 mL) and water (200 mL). The organic layer was extracted with an additional portion of ether (100 mL) and the combined organics washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated. To give 2-[2-(2-Hydroxy-ethyl)-phenyl]-ethanol (3.3 g/80%). 1H NMR (400 MHz, CDCl3) δ 7.2 (m, 4H), 3.9 (t, J=6.8 Hz, 4H), 2.95 (t, J=6.8 Hz, 4H). The reaction was left then carefully quenched by the addition of water (ca. 20 mL) The reaction was partitioned between diethyl ether (200 mL) and water (200 mL) The organic layer was extracted with an additional portion of ether (100 mL) the combined organics washed with brine (100 mL) dried over magnesium sulfate filtered concentrated

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

Procedure: To a solution of 2,2′-(1,2-phenylene)diacetic acid (10 g, 51.5 mmol) in THF (100 mL) was added to LAH in THF (90 mL) dropwise, the mixture was refluxed for 18 hours. The mixture was cooled in ice bath and carefully added water (8 mL) dropwise, followed by 1 N NaOH (8 mL), then removed the ice bath added water slowly with stirring until the gray precipitate turns white. The mixture was filtrated and the filtrate was concentrated to give crude 2,2′-(1,2-phenylene)diethanol (8 g, 94%). 1H-NMR (CDCl3): 2.02 (s, 3H), 2.97 (m, 4H), 3.83 (m, 2H), 4.12 (m, 1H), 4.24 (t, 1H), 7.19 (m, 4H). the mixture was refluxed for 18 hours The mixture was cooled in ice bath removed the ice bath added water slowly The mixture was filtrated the filtrate was concentrated

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

Procedure: 2-[2-(2-Hydroxy-ethyl)-phenyl]-ethanol (6.77 g/40 mmol) was dissolved in methylene chloride (100 mL) and cooled to 0° C. Triethylamine (11.0 mL/80 mmol) and methanesulfonyl chloride (5.25 mL/65 mmol) were added sequentially via addition funnel (dropwise). After an hour the reaction was poured into a separatory funnel and sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL). The resulting organic solution was dried over magnesium sulfate, filtered and concentrated. Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride afforded methanesulfonic acid 2-[2-(2-hydroxy-ethyl)-phenyl]-ethyl ester (2.25 g/23%). 1H NMR (400 MHz, CDCl3) δ 7.25 (m, 4H), 4.42 (t, J=7.1 Hz, 2H), 3.88 (m, 2H), 3.15 (t, J=7.1 Hz, 2H), 2.93 (t, J=7.1 Hz, 2H), 2.85 (s, 3H). After an hour the reaction was poured into a separatory funnel sequentially washed with 1 N hydrochloric acid (100 mL), water (100 mL) and saturated aqueous sodium bicarbonate (100 mL) The resulting organic solution was dried over magnesium sulfate filtered concentrated Column chromatography on silica gel (eluting with 0→10% methanol/methylene chloride