4-trimethylsilylbut-3-yn-2-one

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

Procedure: To a mixture of methyl propionylacetate (1.93 mL), 4-trimethylsilyl-3-butyn-2-one (2.65 mL) in MeOH (100 mL) was added ammonium acetate (3.55 g) at room temperature. The mixture was stirred at 60° C. overnight. After cooling, the mixture was concentrated. The residue was diluted with water, and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in EtOAc and the insoluble material was removed by filtration. The filtrate was concentrated and the residue was purified by silica gel column chromatography (NH, EtOAc/hexane) to give the title compound (1.56 g). After cooling the mixture was concentrated The residue was diluted with water the mixture was extracted with EtOAc The organic layer was washed with brine dried over MgSO4 concentrated in vacuo The residue was dissolved in EtOAc the insoluble material was removed by filtration The filtrate was concentrated the residue was purified by silica gel column chromatography (NH, EtOAc/hexane)

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

Procedure: To a mixture of methyl propionylacetate (1.93 mL), 4-trimethylsilyl-3-butyn-2-one (2.65 mL) in MeOH (100 mL) was added ammonium acetate (3.55 g) at room temperature. The mixture was stirred at 60° C. overnight. After cooling, the mixture was concentrated. The residue was diluted with water, and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in EtOAc and the insoluble material was removed by filtration. The filtrate was concentrated and the residue was purified by silica gel column chromatography (NH, EtOAc/hexane) to give the title compound (1.56 g). After cooling the mixture was concentrated The residue was diluted with water the mixture was extracted with EtOAc The organic layer was washed with brine dried over MgSO4 concentrated in vacuo The residue was dissolved in EtOAc the insoluble material was removed by filtration The filtrate was concentrated the residue was purified by silica gel column chromatography (NH, EtOAc/hexane)

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure C. In a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane 10 mL) was added dropwise into a solution of 2-bromo-5-fluoropyridine (1.76 g, 10.00 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C. The resulting solution was stirred for 1 h, then 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of NH4Cl (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.19 equiv) was added batchwise into a solution of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.2 g, 9.27 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. When completed monitored by TLC and LCMS, solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. The resulting solution was dried over anhydrous sodium sulfate and concentrated under vacuum, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid. This compound was prepared The resulting solution was stirred for 2 h at −76° C The reaction was then quenched by the addition of 10 mL of NH4Cl (sat., aq.) The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil The resulting solution was stirred for 2 h at room temperature was concentrated under vacuum The residue was diluted with 20 mL of water The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solids were filtered out The resulting solution was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure C. to a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane, 10 mL) was added into a solution of 2-bromo-5-chloropyridine (1.92 g, 9.98 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C., Stirred for 1 h at this temp., 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solid was dried in an oven under reduced pressure. This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.06 equiv) was added batchwise into a solution of 2-(5-chloropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.5 g, 9.85 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. TLC indicated the reaction completed, the solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil. This compound was prepared The resulting solution was stirred for 2 h at −76° C The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.) The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solid was dried in an oven under reduced pressure This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil The resulting solution was stirred for 2 h at room temperature the solvent was concentrated under vacuum The residue was diluted with 20 mL of water The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solids were filtered out The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure C. to a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane, 10 mL) was added into a solution of 2-bromo-5-chloropyridine (1.92 g, 9.98 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C., Stirred for 1 h at this temp., 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solid was dried in an oven under reduced pressure. This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.06 equiv) was added batchwise into a solution of 2-(5-chloropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.5 g, 9.85 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. TLC indicated the reaction completed, the solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil. This compound was prepared The resulting solution was stirred for 2 h at −76° C The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.) The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solid was dried in an oven under reduced pressure This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil The resulting solution was stirred for 2 h at room temperature the solvent was concentrated under vacuum The residue was diluted with 20 mL of water The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solids were filtered out The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was prepared according to a procedure similar to that described in Procedure C. Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-bromo-4-methylpyridine (8.5 g, 49.41 mmol, 1.00 equiv) in tetrahydrofuran (110 mL). This was followed by the addition of n-BuLi (22 mL, 1.20 equiv) dropwise with stirring at −78° C. The resulting solution was stirred for 30 min at −78° C. To this was added 4-(trimethylsilyl)but-3-yn-2-one (7.6 g, 54.19 mmol, 1.10 equiv) dropwise with stirring at −78° C. The resulting solution was warmed slowly to 0° C. and stirred for 10 min at this temperature. The reaction was then quenched by the addition of 10 mL of sat. aq. ammonium chloride. The resulting solution was extracted with 2×40 mL of ethyl acetate and the organic layers combined and dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with petroleum ether:ethyl acetate (5:1). This resulted in 6.5 g (56%) of 2-(4-methylpyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as colourless oil. Into a 250-mL round-bottom flask, was placed a suspension of 2-(4-methylpyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (6.5 g, 27.85 mmol, 1.00 equiv) and potassium fluoride dihydrate (6.6 g, 2.50 equiv) in methanol (50 mL). The resulting solution was stirred for 4 h at 50° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 2×50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 3.5 g (78%) of 2-(4-methylpyridin-2-yl)but-3-yn-2-ol as a pink solid. This compound was prepared Into a 250-mL 3-necked round-bottom flask purged maintained with an inert atmosphere of nitrogen The resulting solution was stirred for 30 min at −78° C with stirring at −78° C The resulting solution was warmed slowly to 0° C. stirred for 10 min at this temperature The reaction was then quenched by the addition of 10 mL of sat. aq. ammonium chloride The resulting solution was extracted with 2×40 mL of ethyl acetate dried over sodium sulfate concentrated under vacuum This resulted in 6.5 g (56%) of 2-(4-methylpyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as colourless oil Into a 250-mL round-bottom flask, was placed The resulting solution was stirred for 4 h at 50° C The resulting mixture was concentrated under vacuum The resulting solution was diluted with 100 mL of ethyl acetate The resulting mixture was washed with 2×50 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 3.5 g (78%) of 2-(4-methylpyridin-2-yl)but-3-yn-2-ol as a pink solid

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

Procedure: To a solution of 3-iodo-1-methyl-1H-pyrazole (378 mg, 1.82 mmol) in dry DCM (15 mL) at 0° C. under an atmosphere of nitrogen, was introduced ethylmagnesium bromide (2.0 mL of a 1.0M solution in THF, 2.0 mmol). After 30 minutes at 0° C., the reaction mixture was warmed to RT for 15 minutes, then introduced to a solution of 4-(trimethylsilyl)but-3-yn-2-one (0.37 ml, 2.18 mmol) in dry DCM (5 ml) at 0° C. under an atmosphere of nitrogen. The reaction mixture was warmed to RT for 16 hr. Following addition of saturated aqueous ammonium chloride (5 ml), the reaction mixture was extracted with DCM (3×5 mL extractions). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by silica gel flash column chromatography (heptane/EtOAc gradient) furnished the title compound as an orange-brown oil: 1H NMR (500 MHz, CDCl3) delta 0.15 (9H, d, J=3.5 Hz), 1.82 (3H, s), 3.18 (1H, s), 3.86 (3H, s), 6.28 (1H, d, J=2.2 Hz), 7.26 (1H, d, J=2.2 Hz); LC-MS: m/z=+222.95 (M+H)+. The reaction mixture was warmed to RT for 16 hr the reaction mixture was extracted with DCM (3×5 mL extractions) The combined organic extracts were dried (Na2SO4) filtered concentrated in vacuo Purification of the residue by silica gel flash column chromatography (heptane/EtOAc gradient)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of isopropylmagnesium chloride lithium chloride complex (1.56 mL of a 1.3M solution in THF, 2.02 mmol) in dry THF (5 mL) at −15° C. under an atmosphere of nitrogen was introduced 2-bromo-5-methyl-1,3,4-oxadiazole (300 mg, 1.84 mmol). The reaction mixture was warmed to −10° C. for 30 minutes. A solution of 4-(trimethylsilyl)but-3-yn-2-one (0.37 ml, 2.21 mmol) in dry THF (5 mL) was added and the reaction mixture warmed to 0° C. for 1 hr. After further warming to RT for 30 minutes, the solution was cooled to 0° C. and saturated aqueous ammonium chloride (5 mL) introduced. The reaction mixture was extracted with DCM (3×10 mL extractions) and the combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash chromatography (Biotage, heptane/EtOAc followed by an EtOAc/MeOH gradient) furnished the title compound as an orange oil: 1H NMR (500 MHz, CDCl3) delta 0.18 (9H, s), 1.95 (3H, s), 2.57 (3H, s), 3.13 (1H, s); LC-MS: m/z=+224.95 (M+H)+. the reaction mixture warmed to 0° C. for 1 hr After further warming to RT for 30 minutes the solution was cooled to 0° C. The reaction mixture was extracted with DCM (3×10 mL extractions) the combined organic extracts were dried (Na2SO4) filtered concentrated in vacuo Purification of the residue by flash chromatography (Biotage, heptane/EtOAc

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-bromo-5-fluoropyridine (1.76 g, 10.00 mmol) in ether (20 mL) maintained under nitrogen at −78° C. was added a solution of s-butyllithium (1.3M in hexane, 10 mL, 13.00 mmol) dropwise. The reaction mixture was then stirred at −78° C. for 1 hr and 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol) was added to the reaction mixture dropwise with stirring at −78° C. The resulting solution was stirred at −78° C. for 2 hr and then quenched by the addition of saturated ammonium chloride solution (5 mL) and water (10 mL). The resulting solution was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified on a silica gel column with ethyl acetate/petroleum ether (1:3) to give 1 g (42%) of the title compound as a yellow oil: LC-MS: m/z=+238 (M+H)+. with stirring at −78° C The resulting solution was stirred at −78° C. for 2 hr quenched by the addition of saturated ammonium chloride solution (5 mL) and water (10 mL) The resulting solution was extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over Na2SO4 filtered concentrated in vacuo The crude residue was purified on a silica gel column with ethyl acetate/petroleum ether (1:3)

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

Procedure: To a mixture of methyl propionylacetate (1.93 mL), 4-trimethylsilyl-3-butyn-2-one (2.65 mL) in MeOH (100 mL) was added ammonium acetate (3.55 g) at room temperature. The mixture was stirred at 60° C. overnight. After cooling, the mixture was concentrated. The residue was diluted with water, and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in EtOAc and the insoluble material was removed by filtration. The filtrate was concentrated and the residue was purified by silica gel column chromatography (NH, EtOAc/hexane) to give the title compound (1.56 g). After cooling the mixture was concentrated The residue was diluted with water the mixture was extracted with EtOAc The organic layer was washed with brine dried over MgSO4 concentrated in vacuo The residue was dissolved in EtOAc the insoluble material was removed by filtration The filtrate was concentrated the residue was purified by silica gel column chromatography (NH, EtOAc/hexane)

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure C. In a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane 10 mL) was added dropwise into a solution of 2-bromo-5-fluoropyridine (1.76 g, 10.00 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C. The resulting solution was stirred for 1 h, then 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of NH4Cl (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.19 equiv) was added batchwise into a solution of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.2 g, 9.27 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. When completed monitored by TLC and LCMS, solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. The resulting solution was dried over anhydrous sodium sulfate and concentrated under vacuum, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid. This compound was prepared The resulting solution was stirred for 2 h at −76° C The reaction was then quenched by the addition of 10 mL of NH4Cl (sat., aq.) The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil The resulting solution was stirred for 2 h at room temperature was concentrated under vacuum The residue was diluted with 20 mL of water The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solids were filtered out The resulting solution was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure C. to a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane, 10 mL) was added into a solution of 2-bromo-5-chloropyridine (1.92 g, 9.98 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C., Stirred for 1 h at this temp., 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solid was dried in an oven under reduced pressure. This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.06 equiv) was added batchwise into a solution of 2-(5-chloropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.5 g, 9.85 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. TLC indicated the reaction completed, the solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil. This compound was prepared The resulting solution was stirred for 2 h at −76° C The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.) The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solid was dried in an oven under reduced pressure This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil The resulting solution was stirred for 2 h at room temperature the solvent was concentrated under vacuum The residue was diluted with 20 mL of water The resulting solution was extracted with 3×20 mL of ethyl acetate The resulting mixture was washed with 1×20 mL of brine The solids were filtered out The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil