2-[2-(hydroxymethyl)phenyl]ethanol

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

Procedure: Manganese(IV) oxide (1.43 g) was added to a solution of 2-(2-hydroxymethyl-phenyl)-ethanol (0.5 g) in dichloromethane (25 mL) and stirred for 18 hours under nitrogen. The reaction was filtered through celite, the filter pad washed with dichloromethane (2×20 mL), and the combined filtrates evaporated. Purification on silica, eluting with a gradient of iso-hexane:ethyl acetate [1:0 to 4:1], afforded the subtitle compound as a yellow oil (263 mg). The reaction was filtered through celite the filter pad washed with dichloromethane (2×20 mL) the combined filtrates evaporated Purification on silica eluting with a gradient of iso-hexane

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Borane-tetrahydrofuran complex (1M solution in tetrahydrofuran, 100 mL) was added dropwise over 10 minutes, to a solution of 2-carboxymethyl-benzoic acid (6 g) in dry tetrahydrofuran (100 mL) at 0° C., under nitrogen. The resulting mixture was stirred at 0-5° C. for 20 minutes, then warmed to room temperature for 1 hour. Saturated citric acid solution (150 mL) was added and the reaction concentrated to ˜150 mL. The aqueous phase was extracted with ethyl acetate (3×150 mL). The combined organics were washed sequentially with 1M aqueous sodium hydroxide solution (150 mL), water (150 mL), brine (150 mL), dried (sodium sulfate) and evaporated to give the subtitle compound as yellow oil (3.5 g). warmed to room temperature for 1 hour the reaction concentrated to ˜150 mL The aqueous phase was extracted with ethyl acetate (3×150 mL) The combined organics were washed sequentially with 1M aqueous sodium hydroxide solution (150 mL), water (150 mL), brine (150 mL) dried (sodium sulfate) evaporated

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

Procedure: To a solution of 2-(carboxymethyl)benzoic acid (9 g, 0.05 mol) in THF (200 mL) was added to LAH in THF (250 mL) dropwise, the mixture was refluxed for 18 hours. The mixture was cooled in ice bath and carefully added water dropwise, followed by 50% NaOH (150 mL), then removed the ice bath and 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-(hydroxymethyl)phenyl)ethanol (6 g, 80%). 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: Mix 2-(2-hydroxymethyl-phenyl)-ethanol (12.0 g, 78.8 mmol) and collidine (23 mL, 0.17 mol) and treat with lithium chloride (7.35 g, 0.173 mmol) in dimethylformamide (125 mL). Cool in an ice bath and treat, by dropwise addition, with mesyl chloride (13.4 mL). Stir at 0° C. for 4 hours, partition between ice water (300 mL) and a 1:1 mixture of ether:pentane (2×400 mL). Wash the organic layer with a saturated solution of CuSO4 (2×200 mL), dry (MgSO4) and purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate) to give the title compound as a pale yellow oil (8.8 g, 45%). Cool in an ice bath partition between ice water (300 mL) a 1:1 mixture of ether Wash the organic layer with a saturated solution of CuSO4 (2×200 mL) dry (MgSO4) purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate)

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

Procedure: Dissolve homophthalic acid (22.2 g, 0.123 mmol) in tetrahydrofuran (250 mL) and add dropwise at room temperature to a slurry of lithium aluminum hydride (15.5 g, 0.407 mol) in tetrahydrofuran (500 mL). Heat at reflux for 18 hours, cool in an ice bath and carefully add, by dropwise addition, water (16 mL), followed by 50% sodium hydroxide (16 mL). Remove the ice bath, add water slowly with stirring and stir until the gray precipitate turns white and evolution of gas ceases. Filter, wash solids with methylene chloride, dry (MgSO4) and evaporate the solvent in vacuo to give 2-(2-hydroxymethyl-phenyl)-ethanol as a viscous oil (18.4 g, 98%). Heat at reflux for 18 hours cool in an ice bath Remove the ice bath add water slowly stir until the gray precipitate Filter wash solids with methylene chloride dry (MgSO4) evaporate the solvent in vacuo

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

Procedure: Mix 2-(2-hydroxymethyl-phenyl)-ethanol (12.0 g, 78.8 mmol) and collidine (23 mL, 0.17 mol) and treat with lithium chloride (7.35 g, 0.173 mmol) in dimethylformamide (125 mL). Cool in an ice bath and treat, by dropwise addition, with mesyl chloride (13.4 mL). Stir at 0° C. for 4 hours, partition between ice water (300 mL) and a 1:1 mixture of ether:pentane (2×400 mL). Wash the organic layer with a saturated solution of CuSO4 (2×200 mL), dry (MgSO4) and purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate) to give the title compound as a pale yellow oil (8.8 g, 45%). Cool in an ice bath partition between ice water (300 mL) a 1:1 mixture of ether Wash the organic layer with a saturated solution of CuSO4 (2×200 mL) dry (MgSO4) purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate)

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

Procedure: Dissolve homophthalic acid (22.2 g, 0.123 mmol) in tetrahydrofuran (250 mL) and add dropwise at room temperature to a slurry of lithium aluminum hydride (15.5 g, 0.407 mol) in tetrahydrofuran (500 mL). Heat at reflux for 18 hours, cool in an ice bath and carefully add, by dropwise addition, water (16 mL), followed by 50% sodium hydroxide (16 mL). Remove the ice bath, add water slowly with stirring and stir until the gray precipitate turns white and evolution of gas ceases. Filter, wash solids with methylene chloride, dry (MgSO4) and evaporate the solvent in vacuo to give 2-(2-hydroxymethyl-phenyl)-ethanol as a viscous oil (18.4 g, 98%). Heat at reflux for 18 hours cool in an ice bath Remove the ice bath add water slowly stir until the gray precipitate Filter wash solids with methylene chloride dry (MgSO4) evaporate the solvent in vacuo

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

Procedure: To a solution of 2-(carboxymethyl)benzoic acid (9 g, 0.05 mol) in THF (200 mL) was added to LAH in THF (250 mL) dropwise, the mixture was refluxed for 18 hours. The mixture was cooled in ice bath and carefully added water dropwise, followed by 50% NaOH (150 mL), then removed the ice bath and 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-(hydroxymethyl)phenyl)ethanol (6 g, 80%). 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: Mix 2-(2-hydroxymethyl-phenyl)-ethanol (12.0 g, 78.8 mmol) and collidine (23 mL, 0.17 mol) and treat with lithium chloride (7.35 g, 0.173 mmol) in dimethylformamide (125 mL). Cool in an ice bath and treat, by dropwise addition, with mesyl chloride (13.4 mL). Stir at 0° C. for 4 hours, partition between ice water (300 mL) and a 1:1 mixture of ether:pentane (2×400 mL). Wash the organic layer with a saturated solution of CuSO4 (2×200 mL), dry (MgSO4) and purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate) to give the title compound as a pale yellow oil (8.8 g, 45%). Cool in an ice bath partition between ice water (300 mL) a 1:1 mixture of ether Wash the organic layer with a saturated solution of CuSO4 (2×200 mL) dry (MgSO4) purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate)

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

Procedure: Dissolve homophthalic acid (22.2 g, 0.123 mmol) in tetrahydrofuran (250 mL) and add dropwise at room temperature to a slurry of lithium aluminum hydride (15.5 g, 0.407 mol) in tetrahydrofuran (500 mL). Heat at reflux for 18 hours, cool in an ice bath and carefully add, by dropwise addition, water (16 mL), followed by 50% sodium hydroxide (16 mL). Remove the ice bath, add water slowly with stirring and stir until the gray precipitate turns white and evolution of gas ceases. Filter, wash solids with methylene chloride, dry (MgSO4) and evaporate the solvent in vacuo to give 2-(2-hydroxymethyl-phenyl)-ethanol as a viscous oil (18.4 g, 98%). Heat at reflux for 18 hours cool in an ice bath Remove the ice bath add water slowly stir until the gray precipitate Filter wash solids with methylene chloride dry (MgSO4) evaporate the solvent in vacuo

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

Procedure: Mix 2-(2-hydroxymethyl-phenyl)-ethanol (12.0 g, 78.8 mmol) and collidine (23 mL, 0.17 mol) and treat with lithium chloride (7.35 g, 0.173 mmol) in dimethylformamide (125 mL). Cool in an ice bath and treat, by dropwise addition, with mesyl chloride (13.4 mL). Stir at 0° C. for 4 hours, partition between ice water (300 mL) and a 1:1 mixture of ether:pentane (2×400 mL). Wash the organic layer with a saturated solution of CuSO4 (2×200 mL), dry (MgSO4) and purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate) to give the title compound as a pale yellow oil (8.8 g, 45%). Cool in an ice bath partition between ice water (300 mL) a 1:1 mixture of ether Wash the organic layer with a saturated solution of CuSO4 (2×200 mL) dry (MgSO4) purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate)

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

Procedure: Dissolve homophthalic acid (22.2 g, 0.123 mmol) in tetrahydrofuran (250 mL) and add dropwise at room temperature to a slurry of lithium aluminum hydride (15.5 g, 0.407 mol) in tetrahydrofuran (500 mL). Heat at reflux for 18 hours, cool in an ice bath and carefully add, by dropwise addition, water (16 mL), followed by 50% sodium hydroxide (16 mL). Remove the ice bath, add water slowly with stirring and stir until the gray precipitate turns white and evolution of gas ceases. Filter, wash solids with methylene chloride, dry (MgSO4) and evaporate the solvent in vacuo to give 2-(2-hydroxymethyl-phenyl)-ethanol as a viscous oil (18.4 g, 98%). Heat at reflux for 18 hours cool in an ice bath Remove the ice bath add water slowly stir until the gray precipitate Filter wash solids with methylene chloride dry (MgSO4) evaporate the solvent in vacuo