2-[4-(2-hydroxyethyl)phenyl]ethanol

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: tert-Butyldimethylchlorosilane (9.68 mL) was added to a solution of 2,2′-(1,4-phenylene)diethanol (example 5, step a) (8.64 g) and imidazole (10.21 g) in dry DMF (100 mL) cooled in an ice bath. After 45 min, the reaction mixture was diluted with ethyl acetate, washed three times with water and evaporated in vacuo. Purification was by silica gel chromatography, eluting with 5:1 isohexane:ethyl acetate to give the subtitled compound as a colourless oil. Yield 6.20 g. cooled in an ice bath washed three times with water evaporated in vacuo Purification eluting with 5:1 isohexane

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

Procedure: Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 80 mL) was added over 20 min to a stirred solution of 2,2′-(1,4-phenylene)diacetic acid (10.20 g) in tetrahydrofuran (100 mL) cooled in an ice bath. After 16 h, the reaction mixture was carefully quenched with methanol (40 mL). The solution was evaporated in vacuo and the resulting gum was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The ethyl acetate solution was separated, dried over magnesium sulphate, filtered and evaporated in vacuo to give the subtitled compound as gum. Yield 8.64 g. cooled in an ice bath the reaction mixture was carefully quenched with methanol (40 mL) The solution was evaporated in vacuo the resulting gum was partitioned between ethyl acetate and saturated aqueous ammonium chloride The ethyl acetate solution was separated dried over magnesium sulphate filtered evaporated in vacuo

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

Procedure: Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 80 mL) was added over 20 min to a stirred solution of 2,2′-(1,4-phenylene)diacetic acid (10.20 g) in tetrahydrofuran (100 mL) cooled in an ice bath. After 16 h, the reaction mixture was carefully quenched with methanol (40 mL). The solution was evaporated in vacuo and the resulting gum was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The ethyl acetate solution was separated, dried over magnesium sulphate, filtered and evaporated in vacuo to give the subtitled compound as gum. Yield 8.64 g. cooled in an ice bath the reaction mixture was carefully quenched with methanol (40 mL) The solution was evaporated in vacuo the resulting gum was partitioned between ethyl acetate and saturated aqueous ammonium chloride The ethyl acetate solution was separated dried over magnesium sulphate filtered evaporated in vacuo

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

Procedure: To a stirred solution of the intermediate from Step A in THF (50 mL) was added DABCO (1.51 g, 13.5 mmol) and then p-toluenesulfonyl chloride (50 mL). The resulting mixture was stirred overnight at room temperature and then filtered to remove precipitated hydrochloride salts. The filtrate was concentrated under reduced pressure and DCM (50 mL) was added to the residue. The organic layer was then washed with water (1×100 mL), saturated NaCl (1×100 mL), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. The resulting material was purified by silica gel chromatography (70% EtOAc/hexane) to afford 1.25 g of the title intermediate (43% yield). filtered to remove precipitated hydrochloride salts The filtrate was concentrated under reduced pressure and DCM (50 mL) was added to the residue The organic layer was then washed with water (1×100 mL), saturated NaCl (1×100 mL) dried over magnesium sulfate filtered the solvent removed under reduced pressure The resulting material was purified by silica gel chromatography (70% EtOAc/hexane)

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

Procedure: To a stirred solution of (4-carboxymethylphenyl)acetic acid (1.0 g, 5.15 mmol) in THF (100 mL) was slowly added borane dimethyl sulfide (2.3 mL, 30.9 mmol) and the resulting mixture was stirred overnight (˜18 hours). The reaction was then quenched by slowly adding 1N HCl (100 mL). The resulting mixture was then extracted with EtOAc (3×100 mL). The combined organic layers were washed with saturated NaCl (1×100 mL), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure to provide 750 mg of the title intermediate (87% yield), which was used without further purification. The reaction was then quenched by slowly adding 1N HCl (100 mL) The resulting mixture was then extracted with EtOAc (3×100 mL) The combined organic layers were washed with saturated NaCl (1×100 mL) dried over magnesium sulfate filtered the solvent removed under reduced pressure

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

Procedure: To a stirred solution of the intermediate from Step A in THF (50 mL) was added DABCO (1.51 g, 13.5 mmol) and then p-toluenesulfonyl chloride (50 mL). The resulting mixture was stirred overnight at room temperature and then filtered to remove precipitated hydrochloride salts. The filtrate was concentrated under reduced pressure and DCM (50 mL) was added to the residue. The organic layer was then washed with water (1×100 mL), saturated NaCl (1×100 mL), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. The resulting material was purified by silica gel chromatography (70% EtOAc/hexane) to afford 1.25 g of the title intermediate (43% yield). filtered to remove precipitated hydrochloride salts The filtrate was concentrated under reduced pressure and DCM (50 mL) was added to the residue The organic layer was then washed with water (1×100 mL), saturated NaCl (1×100 mL) dried over magnesium sulfate filtered the solvent removed under reduced pressure The resulting material was purified by silica gel chromatography (70% EtOAc/hexane)

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

Procedure: To a stirred solution of (4-carboxymethylphenyl)acetic acid (1.0 g, 5.15 mmol) in THF (100 mL) was slowly added borane dimethyl sulfide (2.3 mL, 30.9 mmol) and the resulting mixture was stirred overnight (˜18 hours). The reaction was then quenched by slowly adding 1N HCl (100 mL). The resulting mixture was then extracted with EtOAc (3×100 mL). The combined organic layers were washed with saturated NaCl (1×100 mL), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure to provide 750 mg of the title intermediate (87% yield), which was used without further purification. The reaction was then quenched by slowly adding 1N HCl (100 mL) The resulting mixture was then extracted with EtOAc (3×100 mL) The combined organic layers were washed with saturated NaCl (1×100 mL) dried over magnesium sulfate filtered the solvent removed under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: tert-Butyldimethylchlorosilane (9.68 mL) was added to a solution of 2,2′-(1,4-phenylene)diethanol (example 5, step a) (8.64 g) and imidazole (10.21 g) in dry DMF (100 mL) cooled in an ice bath. After 45 min, the reaction mixture was diluted with ethyl acetate, washed three times with water and evaporated in vacuo. Purification was by silica gel chromatography, eluting with 5:1 isohexane:ethyl acetate to give the subtitled compound as a colourless oil. Yield 6.20 g. cooled in an ice bath washed three times with water evaporated in vacuo Purification eluting with 5:1 isohexane

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

Procedure: Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 80 mL) was added over 20 min to a stirred solution of 2,2′-(1,4-phenylene)diacetic acid (10.20 g) in tetrahydrofuran (100 mL) cooled in an ice bath. After 16 h, the reaction mixture was carefully quenched with methanol (40 mL). The solution was evaporated in vacuo and the resulting gum was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The ethyl acetate solution was separated, dried over magnesium sulphate, filtered and evaporated in vacuo to give the subtitled compound as gum. Yield 8.64 g. cooled in an ice bath the reaction mixture was carefully quenched with methanol (40 mL) The solution was evaporated in vacuo the resulting gum was partitioned between ethyl acetate and saturated aqueous ammonium chloride The ethyl acetate solution was separated dried over magnesium sulphate filtered evaporated in vacuo

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

Procedure: To a stirred solution of the intermediate from Step A in THF (50 mL) was added DABCO (1.51 g, 13.5 mmol) and then p-toluenesulfonyl chloride (50 mL). The resulting mixture was stirred overnight at room temperature and then filtered to remove precipitated hydrochloride salts. The filtrate was concentrated under reduced pressure and DCM (50 mL) was added to the residue. The organic layer was then washed with water (1×100 mL), saturated NaCl (1×100 mL), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. The resulting material was purified by silica gel chromatography (70% EtOAc/hexane) to afford 1.25 g of the title intermediate (43% yield). filtered to remove precipitated hydrochloride salts The filtrate was concentrated under reduced pressure and DCM (50 mL) was added to the residue The organic layer was then washed with water (1×100 mL), saturated NaCl (1×100 mL) dried over magnesium sulfate filtered the solvent removed under reduced pressure The resulting material was purified by silica gel chromatography (70% EtOAc/hexane)