3-(4-fluorophenyl)prop-2-yn-1-ol

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

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

Procedure: A solution of 3-(4-fluorophenyl)prop-2-yn-1-ol (1 g, 6.80 mmol) in DCM (13.6 mL) under N2 was cooled in a ice bath at 0° C. 2.70 g (8.2 mmol, loading 3 mmol/g) of triphenylphosphine polymer supported was then added followed by 2.70 g (8.2 mmol) of carbon tetrabromide. The reaction mixture was stirred 15 min at 0° C. and warmed to room temperature for 90 min. After filtration through celite, the solvent was evaporated under reduce pressure. The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent) to afford 1.44 g of 1-(3-bromoprop-1-ynyl)-4-fluorobenzene as a yellow oil (Yield: 99%). warmed to room temperature for 90 min After filtration through celite the solvent was evaporated The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent)

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 4-fluoro-1-iodobenzene (11.0 g, 50.0 mmol) in anhydrous tetrahydrofuran (90 mL) was degassed and copper(I) iodide (0.29 g, 1.5 mmol), tetrakis(triphenylphosphine)palladium (1.75 g, 1.5 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (9.25 g, 60.0 mmol) were added. The reaction solution was degassed again and propargyl alcohol (3.5 mL, 60.0 mmol) was added dropwise under inert atmosphere at ambient temperature. The obtained yellow suspension was stirred at ambient temperature overnight, then treated with brine (10 mL) and acidified with 2 M hydrochloric acid to pH˜2. The phases were separated and the aqueous phase was extracted with ether (4×50 mL). The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo yielding brown solid. The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) and the obtained light yellow solid was crystallized from hexane yielding 3-(4-fluorophenyl)prop-2-yn-1-ol as light yellow needles. The reaction solution was degassed again The phases were separated the aqueous phase was extracted with ether (4×50 mL) The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL) dried over anhydrous magnesium sulfate concentrated in vacuo yielding brown solid The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) the obtained light yellow solid was crystallized from hexane

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

Procedure: A solution of 4-fluoro-1-iodobenzene (11.0 g, 50.0 mmol) in anhydrous tetrahydrofuran (90 mL) was degassed and copper(I) iodide (0.29 g, 1.5 mmol), tetrakis(triphenylphosphine)palladium (1.75 g, 1.5 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (9.25 g, 60.0 mmol) were added. The reaction solution was degassed again and propargyl alcohol (3.5 mL, 60.0 mmol) was added dropwise under inert atmosphere at ambient temperature. The obtained yellow suspension was stirred at ambient temperature overnight, then treated with brine (10 mL) and acidified with 2 M hydrochloric acid to pH˜2. The phases were separated and the aqueous phase was extracted with ether (4×50 mL). The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo yielding brown solid. The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) and the obtained light yellow solid was crystallized from hexane yielding 3-(4-fluorophenyl)prop-2-yn-1-ol as light yellow needles. The reaction solution was degassed again The phases were separated the aqueous phase was extracted with ether (4×50 mL) The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL) dried over anhydrous magnesium sulfate concentrated in vacuo yielding brown solid The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) the obtained light yellow solid was crystallized from hexane

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

Procedure: A solution of 4-fluoro-1-iodobenzene (11.0 g, 50.0 mmol) in anhydrous tetrahydrofuran (90 mL) was degassed and copper(I) iodide (0.29 g, 1.5 mmol), tetrakis(triphenylphosphine)palladium (1.75 g, 1.5 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (9.25 g, 60.0 mmol) were added. The reaction solution was degassed again and propargyl alcohol (3.5 mL, 60.0 mmol) was added dropwise under inert atmosphere at ambient temperature. The obtained yellow suspension was stirred at ambient temperature overnight, then treated with brine (10 mL) and acidified with 2 M hydrochloric acid to pH˜2. The phases were separated and the aqueous phase was extracted with ether (4×50 mL). The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo yielding brown solid. The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) and the obtained light yellow solid was crystallized from hexane yielding 3-(4-fluorophenyl)prop-2-yn-1-ol as light yellow needles. The reaction solution was degassed again The phases were separated the aqueous phase was extracted with ether (4×50 mL) The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL) dried over anhydrous magnesium sulfate concentrated in vacuo yielding brown solid The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) the obtained light yellow solid was crystallized from hexane

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

Procedure: A solution of 3-(4-fluorophenyl)prop-2-yn-1-ol (1 g, 6.80 mmol) in DCM (13.6 mL) under N2 was cooled in a ice bath at 0° C. 2.70 g (8.2 mmol, loading 3 mmol/g) of triphenylphosphine polymer supported was then added followed by 2.70 g (8.2 mmol) of carbon tetrabromide. The reaction mixture was stirred 15 min at 0° C. and warmed to room temperature for 90 min. After filtration through celite, the solvent was evaporated under reduce pressure. The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent) to afford 1.44 g of 1-(3-bromoprop-1-ynyl)-4-fluorobenzene as a yellow oil (Yield: 99%). warmed to room temperature for 90 min After filtration through celite the solvent was evaporated The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent)

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

Procedure: A solution of 3-(4-fluorophenyl)prop-2-yn-1-ol (1 g, 6.80 mmol) in DCM (13.6 mL) under N2 was cooled in a ice bath at 0° C. 2.70 g (8.2 mmol, loading 3 mmol/g) of triphenylphosphine polymer supported was then added followed by 2.70 g (8.2 mmol) of carbon tetrabromide. The reaction mixture was stirred 15 min at 0° C. and warmed to room temperature for 90 min. After filtration through celite, the solvent was evaporated under reduce pressure. The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent) to afford 1.44 g of 1-(3-bromoprop-1-ynyl)-4-fluorobenzene as a yellow oil (Yield: 99%). warmed to room temperature for 90 min After filtration through celite the solvent was evaporated The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent)

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

Procedure: A solution of 4-fluoro-1-iodobenzene (11.0 g, 50.0 mmol) in anhydrous tetrahydrofuran (90 mL) was degassed and copper(I) iodide (0.29 g, 1.5 mmol), tetrakis(triphenylphosphine)palladium (1.75 g, 1.5 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (9.25 g, 60.0 mmol) were added. The reaction solution was degassed again and propargyl alcohol (3.5 mL, 60.0 mmol) was added dropwise under inert atmosphere at ambient temperature. The obtained yellow suspension was stirred at ambient temperature overnight, then treated with brine (10 mL) and acidified with 2 M hydrochloric acid to pH˜2. The phases were separated and the aqueous phase was extracted with ether (4×50 mL). The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo yielding brown solid. The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) and the obtained light yellow solid was crystallized from hexane yielding 3-(4-fluorophenyl)prop-2-yn-1-ol as light yellow needles. The reaction solution was degassed again The phases were separated the aqueous phase was extracted with ether (4×50 mL) The combined organic phases were washed with water (3×30 mL) and brine (2×30 mL) dried over anhydrous magnesium sulfate concentrated in vacuo yielding brown solid The residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 90:10) the obtained light yellow solid was crystallized from hexane

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

Procedure: To a mixture of 4-fluoroiodobenzene (710.0 mg, 3.82 mmol), bistriphenylphosphine palladium chloride (27.0 mg, 0.038 mmol), CuI (3.64 mg, 0.019 mmol) and propargyl alcohol (214.0 mg, 3.82 mmol), was added diisopropylamine (6.1 mL, 1.6 mL/mmol) under nitrogen atmosphere. The reaction mixture was stirred at r.t. for 6 h. After the completion of the reaction as confirmed by TLC, the crude product was extracted with ethylacetate (50 mL). The organic layer was washed with 10% HCl (20 mL), dried over Na2SO4 and concentrated in vacuo to afford the crude compound which was purified by column chromatography (silica gel, 2:8 EtOAc:Pet.Ether) to afford 3-(4-fluoro-phenyl)-prop-2-yn-1-ol (366.0 mg, 64%) as a viscous oil. After the completion of the reaction the crude product was extracted with ethylacetate (50 mL) The organic layer was washed with 10% HCl (20 mL) dried over Na2SO4 concentrated in vacuo to afford the crude compound which was purified by column chromatography (silica gel, 2:8 EtOAc:Pet.Ether)

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

Procedure: A solution of 3-(4-fluorophenyl)prop-2-yn-1-ol (1 g, 6.80 mmol) in DCM (13.6 mL) under N2 was cooled in a ice bath at 0° C. 2.70 g (8.2 mmol, loading 3mmol/g) of triphenylphosphine polymer supported was then added followed by 2.70 g (8.2 mmol) of carbon tetrabromide. The reaction mixture was stirred 15 min at 0° C. and warmed to room temperature for 90 min. After filtration through celite, the solvent was evaporated under reduce pressure. The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent) to afford 1.44 g of 1-(3-bromoprop-1-ynyl)-4-fluorobenzene as a yellow oil (Yield: 99%). warmed to room temperature for 90 min After filtration through celite the solvent was evaporated The crude product was purified by flash chromatography (prepacked 25 g silicagel column, DCM 100% as eluent)