2-bromoethynylbenzene

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: To a solution of sodium hypobromite [prepared by slow addition of bromine (11 ml) to 10M sodium hydroxide solution (50 ml) and crushed ice (100 g)] was added a solution of phenylacetylene (20.4 g, 19.97 mmol) in THF (10 ml). The two phase mixture was stirred vigorously for 5 hours. Saturated aq. ammonium chloride was added and the mixture was extracted with diethyl ether (3×30 ml). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure to provide 1-bromo-2-phenyl-acetylene (36.2 g, 99%) as a yellow oil. 1H-NMR; δ (CDCl3), 7.50 (m). IR: Vmax (neat) 2200 cm-1. the mixture was extracted with diethyl ether (3×30 ml) The combined organic extracts were washed with brine dried over anhydrous magnesium sulfate filtered The solvent was removed under reduced pressure

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

Procedure: In a 10 mL round-bottom flask, 1.02 g of phenylacetylene (10 mmol), 2.1 g bromotrichloromethane (10.5 mmol) and 100 mg of tetra-n-butylammonium fluoride trihydrate (0.316 mmol) were stirred at 24° C. for 15 min. The temperature of the mixture rose to 33° C. in the course of the process. Analysis of the resulting mixture showed that it contained 1.72 g of 1-bromo-2-phenylacetylene (95% yield) and 0.05 g of the unconverted phenylacetylene. rose to 33° C. in the course of the process

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

Procedure: To a solution of sodium hypobromite [prepared by slow addition of bromine (11 ml) to 10M sodium hydroxide solution (50 ml) and crushed ice (100 g)] was added a solution of phenylacetylene (20.4 g, 19.97 mmol) in THF (10 ml). The two phase mixture was stirred vigorously for 5 hours. Saturated aq. ammonium chloride was added and the mixture was extracted with diethyl ether (3×30 ml). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure to provide 1-bromo-2-phenyl-acetylene (36.2 g, 99%) as a yellow oil. 1H-NMR; δ (CDCl3), 7.50 (m). IR: Vmax (neat) 2200 cm-1. the mixture was extracted with diethyl ether (3×30 ml) The combined organic extracts were washed with brine dried over anhydrous magnesium sulfate filtered The solvent was removed under reduced pressure

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

Procedure: To a solution of sodium hypobromite [prepared by slow addition of bromine (11 ml) to 10M sodium hydroxide solution (50 ml) and crushed ice (100 g)] was added a solution of phenylacetylene (20.4 g, 19.97 mmol) in THF (10 ml). The two phase mixture was stirred vigorously for 5 hours. Saturated aq. ammonium chloride was added and the mixture was extracted with diethyl ether (3×30 ml). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure to provide 1-bromo-2-phenyl-acetylene (36.2 g, 99%) as a yellow oil. 1H-NMR; δ (CDCl3), 7.50 (m). IR: Vmax (neat) 2200 cm-1. the mixture was extracted with diethyl ether (3×30 ml) The combined organic extracts were washed with brine dried over anhydrous magnesium sulfate filtered The solvent was removed under reduced pressure

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sealed tube with a teflon screw cap was charged with a mixture of (4-methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amine (200 mg, 0.793 mmol), bromoethynylbenzene (172 mg, 0.951 mmol) Ni(cod)2 (11 mg, 0.040 mmol), dppbz (18 mg, 0.040 mmol) and LiOtBu (127 mg, 1.59 mmol) in dry dioxane (5 ml) and heated to 100° C. for 2 h. Further bromoethynylbenzene (172 mg), Ni(cod)2 (11 mg), dppbz (18 mg) LiOtBu (127 mg, 1.59 mmol) and dry dioxane (2 ml) were added and heating continued for 36 h. The cooled mixture was treated with water and extracted with DCM. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane to afford the title compound as an off-white solid (35 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 8.11 (d, J=5.1 Hz, 1H), 7.87 (s, J=26.8 Hz, 1H), 7.80-7.69 (m, 5H), 7.60-7.49 (m, 3H), 7.33 (d, J=7.2 Hz, 1H), 6.77 (d, J=5.1 Hz, 1H), 2.33 (s, 3H). (ESI+) m/z 353 (M+H)+. Retention time=3.24 mins (method 1). heating extracted with DCM The combined organics were dried over MgSO4 filtered evaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of bromophenylacetylene (5.0 g, 27.6 mmol), potassium carbonate (9.54 g, 69.0 mmol), copper iodide (0.54 g, 2.8 mmol), palladium on carbon (5%, 500 mg), triphenylphosphine (0.72 g, 2.8 mmol), 2-methyl-3-butyn-2-ol (11.6 g, 138 mmol) and 1,2-dimethoxyethane (100 ml) was stirred overnight at 100° C. The product mixture was evaporated. Chromatography on silica gel with petroleum and ethyl acetate (2:1), gave the title compound. Yield 1.06 g (21%). The product mixture was evaporated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of bromophenylacetylene (5.0 g, 27.6 mmol), potassium carbonate (9.54 g, 69.0 mmol), copper iodide (0.54 g, 2.8 mmol), palladium on carbon (5%, 500 mg), triphenylphosphine (0.72 g, 2.8 mmol), 2-methyl-3-butyn-2-ol (11.6 g, 138 mmol) and 1,2-dimethoxyethane (100 ml) was stirred overnight at 100° C. The product mixture was evaporated. Chromatography on silica gel with petroleum and ethyl acetate (2:1), gave the title compound. Yield 1.06 g (21%). The product mixture was evaporated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of bromophenylacetylene (5.0 g, 27.6 mmol), potassium carbonate (9.54 g, 69.0 mmol), copper iodide (0.54 g, 2.8 mmol), palladium on carbon (5%, 500 mg), triphenylphosphine (0.72 g, 2.8 mmol), 2-methyl-3-butyn-2-ol (11.6 g, 138 mmol) and 1,2-dimethoxyethane (100 ml) was stirred overnight at 100° C. The product mixture was evaporated. Chromatography on silica gel with petroleum and ethyl acetate (2:1), gave the title compound. Yield 1.06 g (21%). The product mixture was evaporated