2-[(4-bromophenyl)methyl]-1,3-dioxolane

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-bromobenzyl)-1,3-dioxolane (2.0 g, 8.2 mmol), 3-formylboronic acid (2.45 g, 16.4 mmol), tetrakis-(triphenylphosphine)palladium (0) (0.763 g, 0.66 mmol), and sodium carbonate (1.74 g, 16.4 mmol) in dioxan/water (15 mL/3 mL) in a microwave vessel was degassed in a stream of nitrogen for 10 minutes. The vessel was sealed and heated in the microwave at 125° C. for 30 minutes. The solvent was decanted off, and the solid residues washed with ethyl acetate. The organic phases were combined, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil. The oil was dissolved in methanol (25 mL) and cooled to 0° C. Sodium borohydride (0.393 g, 10.4 mmol) was added portion-wise, and the reaction mixture was stirred at 0° C. for 30 minutes followed by 1 hour at ambient temperature. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic extracts were dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane to afford the title compound (1.16 g, 52%). was degassed in a stream of nitrogen for 10 minutes The vessel was sealed The solvent was decanted off the solid residues washed with ethyl acetate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil cooled to 0° C followed by 1 hour at ambient temperature The reaction mixture was quenched with water extracted twice with ethyl acetate The combined organic extracts were dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane

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

Procedure: To a cooled (0° C.) solution of 4-bromophenethylalcohol (3.9 g, 19.4 mmol) in DCM (50 mL), was added the Dess-Martin reagent (8.22 g, 19.4 mmol). After 10 minutes, the coolant was removed, and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with 10% aqueous potassium carbonate, and the mixture was separated. The aqueous phase was extracted with further DCM (×2), and the combined organic phases were dried with anhydrous magnesium sulphate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil. The oil was dissolved in toluene (35 mL), para-toluenesulfonic acid—monohydrate (0.1 g, 0.52 mmol) and ethylene glycol (5.3 mL, 94.2 mmol) was added, and the mixture heated at reflux under Dean and Stark conditions for 2 hours. The solvent was evaporated at reduced pressure and the residue dissolved in ethyl acetate. The solution was washed with 10% aqueous potassium carbonate, dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil (2.3 g, 49%). the coolant was removed The reaction mixture was quenched with 10% aqueous potassium carbonate the mixture was separated The aqueous phase was extracted with further DCM (×2) the combined organic phases were dried with anhydrous magnesium sulphate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil the mixture heated at reflux under Dean and Stark conditions for 2 hours The solvent was evaporated at reduced pressure the residue dissolved in ethyl acetate The solution was washed with 10% aqueous potassium carbonate dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane

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

Procedure: A solution of 4-bromophenylacetaldehyde from Step 1 (44.5 g, 224 mmol), ethylene glycol (13.7 mL, 246 mmol) and p-toluenesulfonic acid monohydrate (85 mg, 0.45 mmol) in toluene (300 mL) was refluxed for 3 h with concomitant Dean-Stark water trapping. The reaction mixture was then washed successively with 5% aqueous NaHCO3 (2×), water and brine, dried (MgSO4) and concentrated. The residue was distilled under reduced pressure (bp 110°-115° C./0.5 mmHg) to afford the title compound as a colorless liquid (30.0 g, 55%). The reaction mixture was then washed successively with 5% aqueous NaHCO3 (2×), water and brine dried (MgSO4) concentrated The residue was distilled under reduced pressure (bp 110°-115° C./0.5 mmHg)

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-bromobenzyl)-1,3-dioxolane (2.0 g, 8.2 mmol), 3-formylboronic acid (2.45 g, 16.4 mmol), tetrakis-(triphenylphosphine)palladium (0) (0.763 g, 0.66 mmol), and sodium carbonate (1.74 g, 16.4 mmol) in dioxan/water (15 mL/3 mL) in a microwave vessel was degassed in a stream of nitrogen for 10 minutes. The vessel was sealed and heated in the microwave at 125° C. for 30 minutes. The solvent was decanted off, and the solid residues washed with ethyl acetate. The organic phases were combined, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil. The oil was dissolved in methanol (25 mL) and cooled to 0° C. Sodium borohydride (0.393 g, 10.4 mmol) was added portion-wise, and the reaction mixture was stirred at 0° C. for 30 minutes followed by 1 hour at ambient temperature. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic extracts were dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane to afford the title compound (1.16 g, 52%). was degassed in a stream of nitrogen for 10 minutes The vessel was sealed The solvent was decanted off the solid residues washed with ethyl acetate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil cooled to 0° C followed by 1 hour at ambient temperature The reaction mixture was quenched with water extracted twice with ethyl acetate The combined organic extracts were dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-bromobenzyl)-1,3-dioxolane (2.0 g, 8.2 mmol), 3-formylboronic acid (2.45 g, 16.4 mmol), tetrakis-(triphenylphosphine)palladium (0) (0.763 g, 0.66 mmol), and sodium carbonate (1.74 g, 16.4 mmol) in dioxan/water (15 mL/3 mL) in a microwave vessel was degassed in a stream of nitrogen for 10 minutes. The vessel was sealed and heated in the microwave at 125° C. for 30 minutes. The solvent was decanted off, and the solid residues washed with ethyl acetate. The organic phases were combined, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil. The oil was dissolved in methanol (25 mL) and cooled to 0° C. Sodium borohydride (0.393 g, 10.4 mmol) was added portion-wise, and the reaction mixture was stirred at 0° C. for 30 minutes followed by 1 hour at ambient temperature. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic extracts were dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane to afford the title compound (1.16 g, 52%). was degassed in a stream of nitrogen for 10 minutes The vessel was sealed The solvent was decanted off the solid residues washed with ethyl acetate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil cooled to 0° C followed by 1 hour at ambient temperature The reaction mixture was quenched with water extracted twice with ethyl acetate The combined organic extracts were dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane

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

Procedure: To a cooled (0° C.) solution of 4-bromophenethylalcohol (3.9 g, 19.4 mmol) in DCM (50 mL), was added the Dess-Martin reagent (8.22 g, 19.4 mmol). After 10 minutes, the coolant was removed, and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with 10% aqueous potassium carbonate, and the mixture was separated. The aqueous phase was extracted with further DCM (×2), and the combined organic phases were dried with anhydrous magnesium sulphate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil. The oil was dissolved in toluene (35 mL), para-toluenesulfonic acid—monohydrate (0.1 g, 0.52 mmol) and ethylene glycol (5.3 mL, 94.2 mmol) was added, and the mixture heated at reflux under Dean and Stark conditions for 2 hours. The solvent was evaporated at reduced pressure and the residue dissolved in ethyl acetate. The solution was washed with 10% aqueous potassium carbonate, dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil (2.3 g, 49%). the coolant was removed The reaction mixture was quenched with 10% aqueous potassium carbonate the mixture was separated The aqueous phase was extracted with further DCM (×2) the combined organic phases were dried with anhydrous magnesium sulphate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil the mixture heated at reflux under Dean and Stark conditions for 2 hours The solvent was evaporated at reduced pressure the residue dissolved in ethyl acetate The solution was washed with 10% aqueous potassium carbonate dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane

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

Procedure: To a cooled (0° C.) solution of 4-bromophenethylalcohol (3.9 g, 19.4 mmol) in DCM (50 mL), was added the Dess-Martin reagent (8.22 g, 19.4 mmol). After 10 minutes, the coolant was removed, and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with 10% aqueous potassium carbonate, and the mixture was separated. The aqueous phase was extracted with further DCM (×2), and the combined organic phases were dried with anhydrous magnesium sulphate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil. The oil was dissolved in toluene (35 mL), para-toluenesulfonic acid—monohydrate (0.1 g, 0.52 mmol) and ethylene glycol (5.3 mL, 94.2 mmol) was added, and the mixture heated at reflux under Dean and Stark conditions for 2 hours. The solvent was evaporated at reduced pressure and the residue dissolved in ethyl acetate. The solution was washed with 10% aqueous potassium carbonate, dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil (2.3 g, 49%). the coolant was removed The reaction mixture was quenched with 10% aqueous potassium carbonate the mixture was separated The aqueous phase was extracted with further DCM (×2) the combined organic phases were dried with anhydrous magnesium sulphate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil the mixture heated at reflux under Dean and Stark conditions for 2 hours The solvent was evaporated at reduced pressure the residue dissolved in ethyl acetate The solution was washed with 10% aqueous potassium carbonate dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane

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

Procedure: A solution of 4-bromophenylacetaldehyde from Step 1 (44.5 g, 224 mmol), ethylene glycol (13.7 mL, 246 mmol) and p-toluenesulfonic acid monohydrate (85 mg, 0.45 mmol) in toluene (300 mL) was refluxed for 3 h with concomitant Dean-Stark water trapping. The reaction mixture was then washed successively with 5% aqueous NaHCO3 (2×), water and brine, dried (MgSO4) and concentrated. The residue was distilled under reduced pressure (bp 110°-115° C./0.5 mmHg) to afford the title compound as a colorless liquid (30.0 g, 55%). The reaction mixture was then washed successively with 5% aqueous NaHCO3 (2×), water and brine dried (MgSO4) concentrated The residue was distilled under reduced pressure (bp 110°-115° C./0.5 mmHg)

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-bromobenzyl)-1,3-dioxolane (2.0 g, 8.2 mmol), 3-formylboronic acid (2.45 g, 16.4 mmol), tetrakis-(triphenylphosphine)palladium (0) (0.763 g, 0.66 mmol), and sodium carbonate (1.74 g, 16.4 mmol) in dioxan/water (15 mL/3 mL) in a microwave vessel was degassed in a stream of nitrogen for 10 minutes. The vessel was sealed and heated in the microwave at 125° C. for 30 minutes. The solvent was decanted off, and the solid residues washed with ethyl acetate. The organic phases were combined, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil. The oil was dissolved in methanol (25 mL) and cooled to 0° C. Sodium borohydride (0.393 g, 10.4 mmol) was added portion-wise, and the reaction mixture was stirred at 0° C. for 30 minutes followed by 1 hour at ambient temperature. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic extracts were dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane to afford the title compound (1.16 g, 52%). was degassed in a stream of nitrogen for 10 minutes The vessel was sealed The solvent was decanted off the solid residues washed with ethyl acetate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil cooled to 0° C followed by 1 hour at ambient temperature The reaction mixture was quenched with water extracted twice with ethyl acetate The combined organic extracts were dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 100% ethyl acetate in iso-hexane

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

Procedure: To a cooled (0° C.) solution of 4-bromophenethylalcohol (3.9 g, 19.4 mmol) in DCM (50 mL), was added the Dess-Martin reagent (8.22 g, 19.4 mmol). After 10 minutes, the coolant was removed, and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with 10% aqueous potassium carbonate, and the mixture was separated. The aqueous phase was extracted with further DCM (×2), and the combined organic phases were dried with anhydrous magnesium sulphate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil. The oil was dissolved in toluene (35 mL), para-toluenesulfonic acid—monohydrate (0.1 g, 0.52 mmol) and ethylene glycol (5.3 mL, 94.2 mmol) was added, and the mixture heated at reflux under Dean and Stark conditions for 2 hours. The solvent was evaporated at reduced pressure and the residue dissolved in ethyl acetate. The solution was washed with 10% aqueous potassium carbonate, dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil (2.3 g, 49%). the coolant was removed The reaction mixture was quenched with 10% aqueous potassium carbonate the mixture was separated The aqueous phase was extracted with further DCM (×2) the combined organic phases were dried with anhydrous magnesium sulphate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil the mixture heated at reflux under Dean and Stark conditions for 2 hours The solvent was evaporated at reduced pressure the residue dissolved in ethyl acetate The solution was washed with 10% aqueous potassium carbonate dried with anhydrous magnesium sulfate the solvent evaporated at reduced pressure The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane