2-[(4-chlorophenyl)methoxy]ethanol

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

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

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

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

Procedure: A solution of N-bromosuccinimide (272 mg, 1.53 mmol) in DCM (2.5 mL) was added to resin-bound triphenylphosphine (510 mg, 1.53 mEquiv, Fluka) in DCM (2.5 mL), and the reaction was stirred at rt for 10 min. A solution of 2-{[(4-chlorophenyl)methyl]oxy}ethanol (129 mg, 0.691 mmol) in DCM (1.5 mL) was added to the reaction, and the residual alcohol was transferred with additional DCM (1.5 mL). The reaction vial was capped, wrapped in aluminum foil, and stirred at rt for 20 h. The reaction was filtered through a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: DCM (fraction 1), 30% EtOAc/hexanes (fraction 2), and 50% EtOAc/hexanes (fraction 3) to give the title compound (98 mg, 57%). The product was characterized by 1H NMR (400 MHz) in CDCl3. The reaction vial was capped stirred at rt for 20 h The reaction was filtered through a SPE cartridge (5 g silica) eluting with the following 10 mL fractions

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethylene glycol (0.084 mL, 1.5 mmol) was added to NaH (38 mg, 1.52 mmol, 95% in oil) in THF (3 mL). 1-(Bromomethyl)-4-chlorobenzene (310 mg, 1.5 mmol) was added to the reaction, and the residual 1-(bromomethyl)-4-chlorobenzene was transferred to the reaction tube with additional THF (1 mL). (Bu)4NI (55 mg, 0.15 mmol) was then added, and the reaction was heated at 60° C. for 18 h and then rt for 4 h. H2O (2 mL) and EtOAc (2 mL) were added, and the layers were separated via pipette. The aqueous layer was extracted with EtOAc (1×1 mL), and the combined organic layers were concentrated. The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: 30% EtOAc/hexanes (fractions 1,2), 50% EtOAc/hexanes (fraction 3), and 75% EtOAc/hexanes (fraction 4) to give the title compound (129 mg, 46%). The product was characterized by 1H NMR (400 MHz) in CDCl3. the layers were separated via pipette The aqueous layer was extracted with EtOAc (1×1 mL) the combined organic layers were concentrated The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethylene glycol (0.084 mL, 1.5 mmol) was added to NaH (38 mg, 1.52 mmol, 95% in oil) in THF (3 mL). 1-(Bromomethyl)-4-chlorobenzene (310 mg, 1.5 mmol) was added to the reaction, and the residual 1-(bromomethyl)-4-chlorobenzene was transferred to the reaction tube with additional THF (1 mL). (Bu)4NI (55 mg, 0.15 mmol) was then added, and the reaction was heated at 60° C. for 18 h and then rt for 4 h. H2O (2 mL) and EtOAc (2 mL) were added, and the layers were separated via pipette. The aqueous layer was extracted with EtOAc (1×1 mL), and the combined organic layers were concentrated. The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: 30% EtOAc/hexanes (fractions 1,2), 50% EtOAc/hexanes (fraction 3), and 75% EtOAc/hexanes (fraction 4) to give the title compound (129 mg, 46%). The product was characterized by 1H NMR (400 MHz) in CDCl3. the layers were separated via pipette The aqueous layer was extracted with EtOAc (1×1 mL) the combined organic layers were concentrated The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethylene glycol (0.084 mL, 1.5 mmol) was added to NaH (38 mg, 1.52 mmol, 95% in oil) in THF (3 mL). 1-(Bromomethyl)-4-chlorobenzene (310 mg, 1.5 mmol) was added to the reaction, and the residual 1-(bromomethyl)-4-chlorobenzene was transferred to the reaction tube with additional THF (1 mL). (Bu)4NI (55 mg, 0.15 mmol) was then added, and the reaction was heated at 60° C. for 18 h and then rt for 4 h. H2O (2 mL) and EtOAc (2 mL) were added, and the layers were separated via pipette. The aqueous layer was extracted with EtOAc (1×1 mL), and the combined organic layers were concentrated. The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: 30% EtOAc/hexanes (fractions 1,2), 50% EtOAc/hexanes (fraction 3), and 75% EtOAc/hexanes (fraction 4) to give the title compound (129 mg, 46%). The product was characterized by 1H NMR (400 MHz) in CDCl3. the layers were separated via pipette The aqueous layer was extracted with EtOAc (1×1 mL) the combined organic layers were concentrated The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethylene glycol (0.084 mL, 1.5 mmol) was added to NaH (38 mg, 1.52 mmol, 95% in oil) in THF (3 mL). 1-(Bromomethyl)-4-chlorobenzene (310 mg, 1.5 mmol) was added to the reaction, and the residual 1-(bromomethyl)-4-chlorobenzene was transferred to the reaction tube with additional THF (1 mL). (Bu)4NI (55 mg, 0.15 mmol) was then added, and the reaction was heated at 60° C. for 18 h and then rt for 4 h. H2O (2 mL) and EtOAc (2 mL) were added, and the layers were separated via pipette. The aqueous layer was extracted with EtOAc (1×1 mL), and the combined organic layers were concentrated. The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: 30% EtOAc/hexanes (fractions 1,2), 50% EtOAc/hexanes (fraction 3), and 75% EtOAc/hexanes (fraction 4) to give the title compound (129 mg, 46%). The product was characterized by 1H NMR (400 MHz) in CDCl3. the layers were separated via pipette The aqueous layer was extracted with EtOAc (1×1 mL) the combined organic layers were concentrated The crude product was purified on a SPE cartridge (5 g silica) eluting with the following 10 mL fractions

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

Procedure: A solution of methanesulfonyl chloride (980 μL, 12.6 mmol) in dry DCM (10 mL) was slowly added to a cooled (0° C.) solution of 2-(4-chloro-benzyloxy)-ethanol (2.14 g, 11.46 mmol) and diisopropyethylamine (2.0 mL, 23 mmol) in dry DCM (10 mL). The reaction mixture was allowed to warm to RT overnight. Water was added and the organic layer was dried (MgSO4) and concentrated. The residue was purified by column chromatography over silica using a gradient of 0-20% diethyl ether/cyclohexane to afford the pure product. the organic layer was dried (MgSO4) concentrated The residue was purified by column chromatography over silica using a gradient of 0-20% diethyl ether/cyclohexane to afford the pure product

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

Procedure: A solution of methanesulfonyl chloride (980 μL, 12.6 mmol) in dry DCM (10 mL) was slowly added to a cooled (0° C.) solution of 2-(4-chloro-benzyloxy)-ethanol (2.14 g, 11.46 mmol) and diisopropyethylamine (2.0 mL, 23 mmol) in dry DCM (10 mL). The reaction mixture was allowed to warm to RT overnight. Water was added and the organic layer was dried (MgSO4) and concentrated. The residue was purified by column chromatography over silica using a gradient of 0-20% diethyl ether/cyclohexane to afford the pure product. the organic layer was dried (MgSO4) concentrated The residue was purified by column chromatography over silica using a gradient of 0-20% diethyl ether/cyclohexane to afford the pure product

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

Procedure: A solution of methanesulfonyl chloride (980 μL, 12.6 mmol) in dry DCM (10 mL) was slowly added to a cooled (0° C.) solution of 2-(4-chloro-benzyloxy)-ethanol (2.14 g, 11.46 mmol) and diisopropyethylamine (2.0 mL, 23 mmol) in dry DCM (10 mL). The reaction mixture was allowed to warm to RT overnight. Water was added and the organic layer was dried (MgSO4) and concentrated. The residue was purified by column chromatography over silica using a gradient of 0-20% diethyl ether/cyclohexane to afford the pure product. the organic layer was dried (MgSO4) concentrated The residue was purified by column chromatography over silica using a gradient of 0-20% diethyl ether/cyclohexane to afford the pure product

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

Procedure: A solution of N-bromosuccinimide (272 mg, 1.53 mmol) in DCM (2.5 mL) was added to resin-bound triphenylphosphine (510 mg, 1.53 mEquiv, Fluka) in DCM (2.5 mL), and the reaction was stirred at rt for 10 min. A solution of 2-{[(4-chlorophenyl)methyl]oxy}ethanol (129 mg, 0.691 mmol) in DCM (1.5 mL) was added to the reaction, and the residual alcohol was transferred with additional DCM (1.5 mL). The reaction vial was capped, wrapped in aluminum foil, and stirred at rt for 20 h. The reaction was filtered through a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: DCM (fraction 1), 30% EtOAc/hexanes (fraction 2), and 50% EtOAc/hexanes (fraction 3) to give the title compound (98 mg, 57%). The product was characterized by 1H NMR (400 MHz) in CDCl3. The reaction vial was capped stirred at rt for 20 h The reaction was filtered through a SPE cartridge (5 g silica) eluting with the following 10 mL fractions