2-(8-bromooctyl)-1,3-dioxolane

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

Procedure: The title compound was prepared as described in Example 1 Step 1 with tert-butyl (3-hydroxyphenyl)(phenyl)methylcarbamate and methyl bromoacetate replacing 3-hydroxybenzophenone and 2-(8-bromooctyl)-1,3-dioxolane, respectively

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 5-(hydroxymethyl)-2-methylphenol (0.57 g, 4.15 mmol) in dimethyl formamide (15 mL), was added 2-(8-bromooctyl)-1,3-dioxolane (1.00 g, 3.77 mmol) and potassium carbonate (0.63 g, 4.57 mmol), and the mixture was stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine, dried (magnesium sulphate), filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane to afford the title compound (0.5 g, 41%). The reaction mixture was cooled to room temperature extracted with ethyl acetate (×3) The combined organic extracts were washed with brine dried (magnesium sulphate) filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of benzyl 3-bromo-5-hydroxybenzoate (2.85 g, 9.22 mmol) in dimethyl formamide (50 mL), was added 2-(8-bromooctyl)-1,3-dioxolane (2.44 g, 9.21 mmol) and potassium carbonate (1.91 g, 13.8 mmol), and the mixture stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine, dried (magnesium sulphate), filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane to afford the title compound (2.94 g, 65%). The reaction mixture was cooled to room temperature extracted with ethyl acetate (×3) The combined organic extracts were washed with brine dried (magnesium sulphate) filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-(8-bromooctyl)-1,3-dioxolane (5 g, 18.85 mmol) in dimethyl formamide (100 mL) was added 3-hydroxybenzaldehyde (2.37 g, 19.42 mmol) and potassium carbonate (5.37 g, 38.83 mmol). The reaction mixture was stirred at 80° C. for 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 0-100% ethyl acetate in iso-hexane to afford the title compound (4.66 g, 78%). extracted with ethyl acetate (×3) The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and brine dried (sodium sulfate) filtered concentrated under reduced pressure The crude material was purified by silica gel column chromatography eluting with 0-100% ethyl acetate in iso-hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(8-Bromooctyl)-1,3-dioxolane (3.89 g, 14.69 mmol) was added to a mixture of 3-hydroxybenzophenone (3 g, 15.13 mmol) and potassium carbonate (4.17 g, 30.21 mmol) in dimethyl formamide (50 mL). The reaction mixture was stirred at 80° C. for 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution and dried (sodium sulfate), filtered, and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 0-100% ethyl acetate in iso-hexane to afford the title compound (4.73 g, 84%). extracted with ethyl acetate (×3) The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution dried (sodium sulfate) filtered concentrated under reduced pressure The crude material was purified by silica gel column chromatography eluting with 0-100% ethyl acetate in iso-hexane

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

Procedure: To a cooled (−78° C.) solution of oxalyl chloride (11.66 g, 92 mmol) in DCM (250 mL), a solution of dimethylsulfoxide (DMSO) (13.0 mL, 183 mmol) in DCM (50 mL) was added over 15 minutes. After a further 5 minutes, a solution of 9-bromononanol (10.25 g, 45.9 mmol) in DCM (50 mL) was added dropwise over 15 minutes. The resulting reaction mixture was stirred at this temperature for 45 minutes. Triethylamine (32 mL, 230 mmol) was added, and the reaction mixture stirred at this temperature for 10 minutes. The coolant was removed and allowed to warm to RT. The reaction mixture was stirred at RT for 40 minutes and then diluted with water. The organic phase was removed and washed with 10% aqueous potassium hydrogen sulfate and dried (magnesium sulfate). The suspension was filtered and the filtrate evaporated under reduced pressure to afford the title compound. The resulting reaction mixture the reaction mixture stirred at this temperature for 10 minutes The coolant was removed The reaction mixture was stirred at RT for 40 minutes diluted with water The organic phase was removed washed with 10% aqueous potassium hydrogen sulfate dried (magnesium sulfate) The suspension was filtered the filtrate evaporated under reduced pressure

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

Procedure: 9-Bromononanal (28.0 g, assumed 120 mmol), ethylene glycol (33.6 mL, 600 mmol) and para-toluenesulphonic acid (2.7 g, 13 mmol) in toluene (210 mL) were heated at reflux for 20 hours. The reaction was cooled to RT and quenched with saturated aqueous sodium bicarbonate solution (300 mL). The resulting mixture was extracted with diethyl ether (2×500 mL). The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution (300 mL), water (300 mL), brine (100 mL), dried (magnesium sulfate), filtered and evaporated under reduced pressure to afford the title compound (25.2 g, 79%). at reflux for 20 hours quenched with saturated aqueous sodium bicarbonate solution (300 mL) The resulting mixture was extracted with diethyl ether (2×500 mL) The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution (300 mL), water (300 mL), brine (100 mL) dried (magnesium sulfate) filtered evaporated under reduced pressure

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

Procedure: The title compound was prepared as described in Example 1 Step 1 with tert-butyl (3-hydroxyphenyl)(phenyl)methylcarbamate and methyl bromoacetate replacing 3-hydroxybenzophenone and 2-(8-bromooctyl)-1,3-dioxolane, respectively

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

Procedure: The title compound was prepared as described in Example 1 Step 1 with tert-butyl (3-hydroxyphenyl)(phenyl)methylcarbamate and methyl bromoacetate replacing 3-hydroxybenzophenone and 2-(8-bromooctyl)-1,3-dioxolane, respectively

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 5-(hydroxymethyl)-2-methylphenol (0.57 g, 4.15 mmol) in dimethyl formamide (15 mL), was added 2-(8-bromooctyl)-1,3-dioxolane (1.00 g, 3.77 mmol) and potassium carbonate (0.63 g, 4.57 mmol), and the mixture was stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine, dried (magnesium sulphate), filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane to afford the title compound (0.5 g, 41%). The reaction mixture was cooled to room temperature extracted with ethyl acetate (×3) The combined organic extracts were washed with brine dried (magnesium sulphate) filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 5-(hydroxymethyl)-2-methylphenol (0.57 g, 4.15 mmol) in dimethyl formamide (15 mL), was added 2-(8-bromooctyl)-1,3-dioxolane (1.00 g, 3.77 mmol) and potassium carbonate (0.63 g, 4.57 mmol), and the mixture was stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine, dried (magnesium sulphate), filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane to afford the title compound (0.5 g, 41%). The reaction mixture was cooled to room temperature extracted with ethyl acetate (×3) The combined organic extracts were washed with brine dried (magnesium sulphate) filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of benzyl 3-bromo-5-hydroxybenzoate (2.85 g, 9.22 mmol) in dimethyl formamide (50 mL), was added 2-(8-bromooctyl)-1,3-dioxolane (2.44 g, 9.21 mmol) and potassium carbonate (1.91 g, 13.8 mmol), and the mixture stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine, dried (magnesium sulphate), filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane to afford the title compound (2.94 g, 65%). The reaction mixture was cooled to room temperature extracted with ethyl acetate (×3) The combined organic extracts were washed with brine dried (magnesium sulphate) filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography eluting with 0-7% ethyl acetate in iso-hexane