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

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

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

Procedure: A mixture of 4-bromoiodobenzene (8.00 g), copper(I) iodide (108 mg), triphenylphosphine (372 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (586 mg), propargyl alcohol (1.84 ml), diisopropylethylamine (19.7 ml) and tetrahydrofuran (100 ml) was stirred at room temperature for 13 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=98:2-90:10) to give the object product (4.34 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=98:2-90:10)

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

Procedure: A mixture of 4-bromoiodobenzene (8.00 g), copper(I) iodide (108 mg), triphenylphosphine (372 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (586 mg), propargyl alcohol (1.84 ml), diisopropylethylamine (19.7 ml) and tetrahydrofuran (100 ml) was stirred at room temperature for 13 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=98:2-90:10) to give the object product (4.34 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=98:2-90:10)

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

Procedure: Sodium methoxide (23 mg, 0.43 mmol) was added to 1M solution of lithium aluminum hydride in tetrahydrofuran (9 mL, 9.0 mmol). The mixture was cooled to 0° C. and a solution of 3-(4-bromophenyl)prop-2-yn-1-ol (1.9 g, 9.0 mmol) in tetrahydrofuran (15 mL) was slowly added. The reaction was stirred for at 0° C. for 3 h; ethyl acetate (2.7 mL, 9.0 mmol) was added and the mixture was stirred for 10 min without cooling. 4-Iodobenzotrifluoride (2.33 g, 8.6 mmol), anhydrous zinc chloride (0.74 g, 5.4 mmol), tris(dibenzylideneacetone)dipalladium chloroform complex (0.19 g, 0.18 mmol) and tri(2-furyl)phosphine (0.17 g, 0.73 mmol) were added, the mixture was evacuated and kept under nitrogen. The mixture was heated at 65° C. for 16 h. Methanol (4.5 mL) was added and the mixture was stirred for additional 1 h. The reaction mixture was diluted with ether (300 mL) and saturated aqueous solution of ammonium chloride (2.5 mL) was added. The mixture was filtered through a pad of silica gel, evaporated in vacuo and the residue was submitted to column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 80:20) affording (E)-3-(4-bromophenyl)-3-(4-trifluoromethylphenyl)-prop-2-en-1-ol. the mixture was stirred for 10 min without cooling the mixture was evacuated The mixture was heated at 65° C. for 16 h Methanol (4.5 mL) was added the mixture was stirred for additional 1 h The reaction mixture was diluted with ether (300 mL) and saturated aqueous solution of ammonium chloride (2.5 mL) was added The mixture was filtered through a pad of silica gel evaporated in vacuo

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

Procedure: 1M Solution of lithium aluminum hydride in tetrahydrofuran (7.9 mL, 7.9 mmol) was added to sodium methoxide (21 mg, 0.396 mmol) under nitrogen. The mixture was cooled to 0° C. and a solution of 3-(4-bromophenyl)-prop-2-yn-1-ol (1.67 g, 7.91 mmol) in dry tetrahydrofuran (12 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 3.5 h; dry ethyl acetate (2.4 mL, 15.8 mmol) was added and the whole mixture was stirred at ambient temperature for 30 min. A degassed solution of 1-chloro-4-iodobenzene (1.89 g, 7.91 mmol) in anhydrous tetrahydrofuran (12 mL), anhydrous zinc chloride (0.65 g, 4.77 mmol), tris(dibenzylidene-acetone)dipalladium chloroform complex (0.165 g, 0.16 mmol) and tri-(2-furyl)phosphine (0.184 g, 0.791 mmol) were added; the mixture was degassed and stirred at 65° C. for 22 h under atmosphere of nitrogen. The suspension was cooled down; methanol (3.5 mL) was added and the mixture was stirred for additional 1 h. The mixture was diluted with ether (40 mL) and saturated aqueous solution of ammonium chloride (2 mL), was filtered through a pad of silica gel and the pad was thoroughly washed with ether (80 mL). the filtrate was evaporated in vacuo and the residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane/ethyl acetate 20:1) affording (E)-3-(4-bromophenyl)-3-(4-chlorophenyl)-prop-2-en-1-ol as yellow oil, which solidified in fridge. the whole mixture was stirred at ambient temperature for 30 min the mixture was degassed stirred at 65° C. for 22 h under atmosphere of nitrogen The suspension was cooled down methanol (3.5 mL) was added the mixture was stirred for additional 1 h The mixture was diluted with ether (40 mL) and saturated aqueous solution of ammonium chloride (2 mL) was filtered through a pad of silica gel the pad was thoroughly washed with ether (80 mL) the filtrate was evaporated in vacuo the residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane/ethyl acetate 20:1)

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

Procedure: Sodium methoxide (0.27 g, 0.5 mmol) was added to 1M solution of lithium aluminum hydride in tetrahydrofuran (12 mL, 12 mmol). The mixture was cooled to 0° C. and a solution of 3-(4-bromophenyl)prop-2-yn-1-ol (0.422 g, 2.0 mmol) in tetrahydrofuran (50 mL) was slowly added. The reaction was stirred for at 0° C. for 3 h, ethyl acetate (2.6 mL, 30 mmol) was added and the mixture was stirred for further 10 min without cooling. Iodobenzene (2.7 g, 13 mmol), anhydrous zinc bromide (1.4 g, 6 mmol), and tris(dibenzylideneacetone)dipalladium chloroform complex (0.50 g, 0.5 mmol) were added and the mixture was evacuated and kept under nitrogen. A solution of tri-tert-butylphosphine in cyclohexane (6.7 mL, 1 mmol) was added and the mixture was heated at 60° C. for 16 h. Methanol (10 mL) was added and the resulting mixture was stirred for additional 1 h. The reaction mixture was poured into water, acidified with hydrochloric acid and extracted with ethyl acetate (3×100 mL). Organic layers were combined, dried with anhydrous sodium sulphate, evaporated in vacuo and the residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 98:2-70:30) affording (E)-3-(4-bromophenyl)-3-phenylprop-2-en-1-ol. the mixture was stirred for further 10 min without cooling the mixture was evacuated the mixture was heated at 60° C. for 16 h the resulting mixture was stirred for additional 1 h extracted with ethyl acetate (3×100 mL) dried with anhydrous sodium sulphate evaporated in vacuo the residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 98:2-70:30)

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

Procedure: To a solution under inert gas of 36.4 g of 3-(4-bromophenyl)-2-propynol (stage A) in 200 ml of ethanol at 5% of toluene, is added 200 ml of toluene, 7.9 g of Wilkinson's reagent and hydrogen at 1900 mbar for 5 hours. It is evaporated at reduced pressure until the obtainment of 45.9 g of raw product that is purified by chromatography on silica by eluting with the compound CH2Cl2/AcOEt 95/5. 30.1 g of expected product is obtained. It is evaporated at reduced pressure until the obtainment of 45.9 g of raw product that is purified by chromatography on silica by eluting with the compound CH2Cl2/AcOEt 95/5

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

Procedure: Sodium methoxide (23 mg, 0.43 mmol) was added to 1 M solution of lithium aluminum hydride in tetrahydrofuran (9 mL, 9.0 mmol). The mixture was cooled to 0° C. and a solution of 3-(4-bromophenyl)prop-2-yn-1-ol (1.9 g, 9.0 mmol) in tetrahydrofuran (15 mL) was slowly added. The reaction was stirred for at 0° C. for 3 h; ethyl acetate (2.7 mL, 9.0 mmol) was added and the mixture was stirred for 10 min without cooling. 4-Iodobenzotrifluoride (2.33 g, 8.6 mmol), anhydrous zinc chloride (0.74 g, 5.4 mmol), tris(dibenzylideneacetone)dipalladium chloroform complex (0.19 g, 0.18 mmol) and tri(2-furyl)phosphine (0.17 g, 0.73 mmol) were added, the mixture was evacuated and kept under nitrogen. The mixture was heated at 65° C. for 16 h. Methanol (4.5 mL) was added and the mixture was stirred for additional 1 h. The reaction mixture was diluted with ether (300 mL) and saturated aqueous solution of ammonium chloride (2.5 mL) was added. The mixture was filtered through a pad of silica gel, evaporated in vacuo and the residue was submitted to column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 80:20) affording (E)-3-(4-bromophenyl)-3-(4-trifluoromethyl phenyl)-prop-2-en-1-ol. the mixture was stirred for 10 min without cooling the mixture was evacuated The mixture was heated at 65° C. for 16 h Methanol (4.5 mL) was added the mixture was stirred for additional 1 h The reaction mixture was diluted with ether (300 mL) and saturated aqueous solution of ammonium chloride (2.5 mL) was added The mixture was filtered through a pad of silica gel evaporated in vacuo

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

Procedure: 1 M Solution of lithium aluminum hydride in tetrahydrofuran (7.9 mL, 7.9 mmol) was added to sodium methoxide (21 mg, 0.396 mmol) under nitrogen. The mixture was cooled to 0° C. and a solution of 3-(4-bromophenyl)-prop-2-yn-1-ol (1.67 g, 7.91 mmol) in dry tetrahydrofuran (12 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 3.5 h; dry ethyl acetate (2.4 mL, 15.8 mmol) was added and the whole mixture was stirred at ambient temperature for 30 min. A degassed solution of 1-chloro-4-iodobenzene (1.89 g, 7.91 mmol) in anhydrous tetrahydrofuran (12 mL), anhydrous zinc chloride (0.65 g, 4.77 mmol), tris(dibenzylidene-acetone)dipalladium chloroform complex (0.165 g, 0.16 mmol) and tri-(2-furyl)phosphine (0.184 g, 0.791 mmol) were added; the mixture was degassed and stirred at 65° C. for 22 h under atmosphere of nitrogen. The suspension was cooled down; methanol (3.5 mL) was added and the mixture was stirred for additional 1 h. The mixture was diluted with ether (40 mL) and saturated aqueous solution of ammonium chloride (2 mL), was filtered through a pad of silica gel and the pad was thoroughly washed with ether (80 mL). the filtrate was evaporated in vacuo and the residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane/ethyl acetate 20:1) affording (E)-3-(4-bromophenyl)-3-(4-chlorophenyl)-prop-2-en-1-ol as yellow oil, which solidified in fridge. the whole mixture was stirred at ambient temperature for 30 min the mixture was degassed stirred at 65° C. for 22 h under atmosphere of nitrogen The suspension was cooled down methanol (3.5 mL) was added the mixture was stirred for additional 1 h The mixture was diluted with ether (40 mL) and saturated aqueous solution of ammonium chloride (2 mL) was filtered through a pad of silica gel the pad was thoroughly washed with ether (80 mL) the filtrate was evaporated in vacuo the residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane/ethyl acetate 20:1)

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

Procedure: Sodium methoxide (0.27 g, 0.5 mmol) was added to 1 M solution of lithium aluminum hydride in tetrahydrofuran (12 mL, 12 mmol). The mixture was cooled to 0° C. and a solution of 3-(4-bromophenyl)prop-2-yn-1-ol (0.422 g, 2.0 mmol) in tetrahydrofuran (50 mL) was slowly added. The reaction was stirred for at 0° C. for 3 h, ethyl acetate (2.6 mL, 30 mmol) was added and the mixture was stirred for further 10 min without cooling. Iodobenzene (2.7 g, 13 mmol), anhydrous zinc bromide (1.4 g, 6 mmol), and tris(dibenzylideneacetone)dipalladium chloroform complex (0.50 g, 0.5 mmol) were added and the mixture was evacuated and kept under nitrogen. A solution of tri-tert-butylphosphine in cyclohexane (6.7 mL, 1 mmol) was added and the mixture was heated at 60° C. for 16 h. Methanol (10 mL) was added and the resulting mixture was stirred for additional 1 h. The reaction mixture was poured into water, acidified with hydrochloric acid and extracted with ethyl acetate (3×100 mL). Organic layers were combined, dried with anhydrous sodium sulphate, evaporated in vacuo and the residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 98:2-70:30) affording (E)-3-(4-bromophenyl)-3-phenylprop-2-en-1-ol. the mixture was stirred for further 10 min without cooling the mixture was evacuated the mixture was heated at 60° C. for 16 h the resulting mixture was stirred for additional 1 h extracted with ethyl acetate (3×100 mL) dried with anhydrous sodium sulphate evaporated in vacuo the residue was purified by column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 98:2-70:30)

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

Procedure: A solution of 1-(4-bromophenyl)-1-propyne-3-ol B (6.58 g, 31.2 mmol) in anhydrous tetrahydrofuran (THF, 66 mL) was chilled in an ice bath. A 65% w/w solution of Red-Al in toluene (PhMe, 18.7 mL, 19.4 g, 62.4 mmol) was added dropwise over 15 minutes. After 1 hour ethyl acetate (EtOAc, 3.0 mL, 2.75 g, 31.2 mmol) was added. The reaction mixture was chilled in a dry-ice/acetone bath. A solution of I2 (12.7 g, 49.9 mmol) in anhydrous THF (66 mL) was added dropwise. The reaction mixture was allowed to slowly warm to room temperature overnight. The reaction was quenched with saturated Na2SO3 and filtered through Celite. The filter cake was washed well with EtOAc. The filtrate was washed with water and brine, dried (MgSO4), filtered, and concentrated. Column chromatography (20% EtOAc/hexanes) provided (Z)-1-(4-bromophenyl)-1-iodopropene-3-ol C (8.82 g, 83%) as a yellow solid. 1H NMR (300 MHz, CDCl3) 1.82 (t, 1H), 4.37 (collapsed dd, 2H), 6.25 (t, 1H), 7.34 (d, 2H), 7.44 (d, 2H). The reaction mixture was chilled in a dry-ice/acetone bath The reaction was quenched with saturated Na2SO3 filtered through Celite The filter cake was washed well with EtOAc The filtrate was washed with water and brine dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 4-bromoiodobenzene (10.0 g, 35.3 mmol) in triethylamine (Et3N, 100 mL) was added propargyl alcohol (2.7 mL, 2.57 g, 45.9 mmol), Cul (0.81 g, 4.24 mmol), and Pd(PPh3)4 (1.63 g, 1.41 mmol). The mixture was stirred overnight, then the reaction mixture was concentrated. Column chromatography (20-35% EtOAc/hexanes) provided 1-(4-bromophenyl)-1-propyne-3-ol B (6.58 g, 88%) as a yellow/orange solid. 1H NMR (300 MHz, CDCl3) 1.77 (t, 1H), 4.48 (d, 2H), 7.29 (d, 2H), 7.45 (d, 2H). the reaction mixture was concentrated