4-(4-chlorophenyl)but-3-yn-2-ol

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

Procedure: To a solution of 4-(4-chloro-phenyl)-but-3-yn-2-ol (3 g, 16.6 mmol), phthalimide (3.7 g, 25.2 mmol, 1.5 eq.) and PPh3 (4.8 g, 18.3 mmol, 1.1 eq.) in 100 mL of THF cooled to 0° C. with an ice bath was added dropwise DEAD (i.e., diethyl azodicarboxylate) (3.1 mL, 19.9 mmol, 1.2 eq.). The ice-bath was removed and the mixture was stirred overnight at room temperature. The THF was evaporated and the residue was stirred with 200 mL of 1:1 ether-hexane mixture for 1 hr. The precipitate was filtered off and the filtrate was concentrated and chromatographed with 15% ethyl acetate-hexane to provide 4.1 g of 2-[3-(4-chloro-phenyl)-1-methyl-prop-2-ynyl]-isoindole-1,3-dione. The ice-bath was removed The THF was evaporated the residue was stirred with 200 mL of 1:1 ether-hexane mixture for 1 hr The precipitate was filtered off the filtrate was concentrated chromatographed with 15% ethyl acetate-hexane

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

Procedure: To a solution of 4-(4-chloro-phenyl)-but-3-yn-2-ol (3 g, 16.6 mmol), phthalimide (3.7 g, 25.2 mmol, 1.5 eq.) and PPh3 (4.8 g, 18.3 mmol, 1.1 eq.) in 100 mL of THF cooled to 0° C. with an ice bath was added dropwise DEAD (i.e., diethyl azodicarboxylate) (3.1 mL, 19.9 mmol, 1.2 eq.). The ice-bath was removed and the mixture was stirred overnight at room temperature. The THF was evaporated and the residue was stirred with 200 mL of 1:1 ether-hexane mixture for 1 hr. The precipitate was filtered off and the filtrate was concentrated and chromatographed with 15% ethyl acetate-hexane to provide 4.1 g of 2-[3-(4-chloro-phenyl)-1-methyl-prop-2-ynyl]-isoindole-1,3-dione. The ice-bath was removed The THF was evaporated the residue was stirred with 200 mL of 1:1 ether-hexane mixture for 1 hr The precipitate was filtered off the filtrate was concentrated chromatographed with 15% ethyl acetate-hexane

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

Procedure: To a solution of 4-chloro iodobenzene (10 g, 42 mmol), 3-butyn-2-ol (6.6 mL, 84 mmol, 2 eq.), and iPr2NH (14.8 mL, 105 mmol, 2.5 eq.) in 200 mL dichloromethane was added CuI (1.6 g, 8.4 mmol, 0.2 eq.) followed by Pd(PPh3)2Cl2 (1.5 g, 2.1 mmol, 5 mol %). The mixture was stirred for 1.5 hr at room temperature, concentrated and diluted with ether. The insoluble components of the mixture were filtered off and the filtrate washed with 1N HCl and brine, dried over MgSO4, filtered, concentrated and chromatographed with 20% ethyl acetate-hexane to provide 7.6 g of 4-(4-chloro-phenyl)-but-3-yn-2-ol. concentrated diluted with ether The insoluble components of the mixture were filtered off the filtrate washed with 1N HCl and brine dried over MgSO4 filtered concentrated chromatographed with 20% ethyl acetate-hexane

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

Procedure: The product prepared in step (d) above (0.05 mol) and dry pyridine (1 ml) are dissolved in dry ether (20 ml) and cooled to 0° C. Phosphorous tribromide (0.025 mol) in 20 ml dry ether is added dropwise with stirring. The reaction mixture is then refluxed for 3 hours. After cooling the mixture to 0°, the excess PBr3 is destroyed by adding crushed ice. The ether layer is washed and dried. The ether is removed and the title product is obtained by distillation. The reaction mixture is then refluxed for 3 hours After cooling the mixture to 0° the excess PBr3 is destroyed by adding crushed ice The ether layer is washed dried The ether is removed

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

Procedure: The product prepared in step (c) above (0.05 mol) and p-toluenesulphonic acid (1 g) dissolved in ethanol (50 ml) is refluxed for 3 hours. After cooling, 2 to 3 g potassium carbonate is added and the mixture is filtered. The ethanol is removed in vacuo and the residue is taken up in ether/water (40 ml/10 ml). The ether layer is washed, dried and the ether is removed in vacuo. The residue is distilled to afford the title compound in almost quantitative yield. is refluxed for 3 hours After cooling the mixture is filtered The ethanol is removed in vacuo The ether layer is washed dried the ether is removed in vacuo The residue is distilled

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

Procedure: To a solution of 4-(4-chloro-phenyl)-but-3-yn-2-ol (3 g, 16.6 mmol), phthalimide (3.7 g, 25.2 mmol, 1.5 eq.) and PPh3 (4.8 g, 18.3 mmol, 1.1 eq.) in 100 mL of THF cooled to 0° C. with an ice bath was added dropwise DEAD (i.e., diethyl azodicarboxylate) (3.1 mL, 19.9 mmol, 1.2 eq.). The ice-bath was removed and the mixture was stirred overnight at room temperature. The THF was evaporated and the residue was stirred with 200 mL of 1:1 ether-hexane mixture for 1 hr. The precipitate was filtered off and the filtrate was concentrated and chromatographed with 15% ethyl acetate-hexane to provide 4.1 g of 2-[3-(4-chloro-phenyl)-1-methyl-prop-2-ynyl]-isoindole-1,3-dione. The ice-bath was removed The THF was evaporated the residue was stirred with 200 mL of 1:1 ether-hexane mixture for 1 hr The precipitate was filtered off the filtrate was concentrated chromatographed with 15% ethyl acetate-hexane

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

Procedure: To a solution of 4-chloro iodobenzene (10 g, 42 mmol), 3-butyn-2-ol (6.6 mL, 84 mmol, 2 eq.), and iPr2NH (14.8 mL, 105 mmol, 2.5 eq.) in 200 mL dichloromethane was added CuI (1.6 g, 8.4 mmol, 0.2 eq.) followed by Pd(PPh3)2Cl2 (1.5 g, 2.1 mmol, 5 mol %). The mixture was stirred for 1.5 hr at room temperature, concentrated and diluted with ether. The insoluble components of the mixture were filtered off and the filtrate washed with 1N HCl and brine, dried over MgSO4, filtered, concentrated and chromatographed with 20% ethyl acetate-hexane to provide 7.6 g of 4-(4-chloro-phenyl)-but-3-yn-2-ol. concentrated diluted with ether The insoluble components of the mixture were filtered off the filtrate washed with 1N HCl and brine dried over MgSO4 filtered concentrated chromatographed with 20% ethyl acetate-hexane