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

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 0.5 g (1.06 mmol) 3-(3,4-Difluoro-benzyl)-6-iodo-1-methyl-1H-quinazoline-2,4-dione and 0.52 g (4.2 mmol) di-isopropyl ethylamine in 15 ml DMF is added bis-triphenylphosphine palladium di-chloride (catalytic) followed by CuI (catalytic). 0.15 g (1.3 mmol) 1-fluoro-4-prop-2-ynyl-benzene is added and the mixture is heated to 70° C. for 6 hours. The mixture is allowed to cool to room temperature and stir overnight. Water is added and the mixture stirred 30 minutes. Filtered and triturated solid in hot EtOAc and filtered. Purified by flash chromatography (EtOAc/hexane eluent). to cool to room temperature the mixture stirred 30 minutes Filtered triturated solid in hot EtOAc filtered Purified by flash chromatography (EtOAc/hexane eluent)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 0.5 g (1.06 mmol) 3-(3,4-Difluoro-benzyl)-6-iodo-1-methyl-1H-quinazoline-2,4-dione and 0.52 g (4.2 mmol) di-isopropyl ethylamine in 15 ml DMF is added bis-triphenylphosphine palladium di-chloride (catalytic) followed by CuI (catalytic). 0.15 g (1.3 mmol) 1-fluoro-4-prop-2-ynyl-benzene is added and the mixture is heated to 70° C. for 6 hours. The mixture is allowed to cool to room temperature and stir overnight. Water is added and the mixture stirred 30 minutes. Filtered and triturated solid in hot EtOAc and filtered. Purified by flash chromatography (EtOAc/hexane eluent). to cool to room temperature the mixture stirred 30 minutes Filtered triturated solid in hot EtOAc filtered Purified by flash chromatography (EtOAc/hexane eluent)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(p-chlorophenyl)-4-hydroxypiperidine (4.00 g) in a mixture of dioxane (30 ml), water (10 ml), and 37 % formalin (2.06 g), there were added a solution of 3-(p-fluorophenyl)-3-hydroxy-1-propyne (2.38 g) in dioxane (5 ml) and a solution of cupric sulfate pentahydrate (127 mg) in water (4 ml) under ice-cooling. The resulting mixture was heated at 80° C for 2 hours and, after cooling, the resulting mixture was filtered and the filtrate was concentrated under reduced pressure and extracted with chloroform. The chloroform extracts were dried over magnesium sulfate. After evaporation of the solvent, the residual oil was chromatographed on silica gel to afford 1-[4-(p-fluorophenyl)-4-hydroxy-2-butynyl]-4-(p-chlorophenyl)-4-hydroxypiperidine (4.56 g) as white crystals, M.P. 145° - 146.2° C. after cooling the resulting mixture was filtered the filtrate was concentrated under reduced pressure extracted with chloroform The chloroform extracts were dried over magnesium sulfate After evaporation of the solvent the residual oil was chromatographed on silica gel

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(2-keto-1-benzimidazolinyl)piperidine (0.625 g) in a mixture of dioxane (10 ml), water (2 ml), and 37% formalin (0.40 g), there were added a solution of 3-(p-fluorophenyl)-3-hydroxy-1-propyne (0.45 g) in dioxane (2 ml) and a solution of cupric sulfate pentahydrate (30 mg) in water (1 ml) under ice-cooling. The resulting mixture was heated at 80° C for 4 hours and, after cooling, the resulting mixture was filtered and the filtrate was concentrated under reduced pressure and extracted with chloroform. The chloroform extracts were dried over magnesium sulfate. After evaporation of the solvent, the residual oil was chromatographed on silica gel to afford 1-[4-(p-fluorophenyl)-4-hydroxy-2-butynyl]-4-(2-keto-1-benzimidazolinyl)piperidine as oily substance. νOHneat or νNHneat 3200 cm-1, νC=Oneat 1680 cm-1. after cooling the resulting mixture was filtered the filtrate was concentrated under reduced pressure extracted with chloroform The chloroform extracts were dried over magnesium sulfate After evaporation of the solvent the residual oil was chromatographed on silica gel

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 200 ml. volume of dry tetrahydrofuran was cooled to -60° C. in a dry ice/acetone bath and then acetylene gas was passed into the solvent until 8.0 g (0.307 mole) had dissolved. The resulting solution was then added to a second 200 ml. portion of dry tetrahydrofuran cooled to -70° C. in a flame-dried 1-liter three-necked, round bottomed reaction flask equipped with magnetic stirrer, addition funnel and nitrogen inlet tube to provide a dry nitrogen atmosphere. To this solution, there was then slowly added 99 ml. of a 2.22 molar solution of n-butyl lithium (0.22 mole) at such a rate that the internal temperature remained below -65° C. After the addition was complete, a solution consisting of 24.82 g (0.20 mole) of p-fluorobenzaldehyde dissolved in 80 ml. of tetrahydrofuran was added at such a rate that the internal temperature again remained below -65° C. The reaction mixture was then stirred at -72° C. for a period of 30 minutes and then allowed to warm up to +5° C. during another 30 minute period. The reaction was then quenched with 80 ml. of water, followed by the addition of anhydrous potassium carbonate to form a pasty mass and an organic supernatant liquid. The organic layer was decanted and combined with two subsequent ether washes of the potassium carbonate mass. The resulting orange solution was then dried over fresh anhydrous potassium carbonate for a period of approximately 16 hours (overnight) and subsequently distilled in vacuo to give 20.5 g (68%) of pure 1-hydroxy-1-(p-fluorophenyl)-2-propyne, b.p. 98°-101° C./8 mm. Hg. A second preparation gave a 92% yield of pure product (b.p. 104° C./9 mm. Hg). had dissolved The resulting solution was then added to a second 200 ml round bottomed reaction flask equipped with magnetic stirrer, addition funnel and nitrogen inlet tube to provide a dry nitrogen atmosphere remained below -65° C After the addition dissolved in 80 ml to warm up to +5° C. during another 30 minute period The reaction was then quenched with 80 ml of water, followed by the addition of anhydrous potassium carbonate to form a pasty mass The organic layer was decanted The resulting orange solution was then dried over fresh anhydrous potassium carbonate for a period of approximately 16 hours (overnight) subsequently distilled in vacuo

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 0.5 g (1.06 mmol) 3-(3,4-Difluoro-benzyl)-6-iodo-1-methyl-1H-quinazoline-2,4-dione and 0.52 g (4.2 mmol) di-isopropyl ethylamine in 15 ml DMF is added bis-triphenylphosphine palladium di-chloride (catalytic) followed by CuI (catalytic). 0.15 g (1.3 mmol) 1-fluoro-4-prop-2-ynyl-benzene is added and the mixture is heated to 70° C. for 6 hours. The mixture is allowed to cool to room temperature and stir overnight. Water is added and the mixture stirred 30 minutes. Filtered and triturated solid in hot EtOAc and filtered. Purified by flash chromatography (EtOAc/hexane eluent). to cool to room temperature the mixture stirred 30 minutes Filtered triturated solid in hot EtOAc filtered Purified by flash chromatography (EtOAc/hexane eluent)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(p-chlorophenyl)-4-hydroxypiperidine (4.00 g) in a mixture of dioxane (30 ml), water (10 ml), and 37 % formalin (2.06 g), there were added a solution of 3-(p-fluorophenyl)-3-hydroxy-1-propyne (2.38 g) in dioxane (5 ml) and a solution of cupric sulfate pentahydrate (127 mg) in water (4 ml) under ice-cooling. The resulting mixture was heated at 80° C for 2 hours and, after cooling, the resulting mixture was filtered and the filtrate was concentrated under reduced pressure and extracted with chloroform. The chloroform extracts were dried over magnesium sulfate. After evaporation of the solvent, the residual oil was chromatographed on silica gel to afford 1-[4-(p-fluorophenyl)-4-hydroxy-2-butynyl]-4-(p-chlorophenyl)-4-hydroxypiperidine (4.56 g) as white crystals, M.P. 145° - 146.2° C. after cooling the resulting mixture was filtered the filtrate was concentrated under reduced pressure extracted with chloroform The chloroform extracts were dried over magnesium sulfate After evaporation of the solvent the residual oil was chromatographed on silica gel

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(2-keto-1-benzimidazolinyl)piperidine (0.625 g) in a mixture of dioxane (10 ml), water (2 ml), and 37% formalin (0.40 g), there were added a solution of 3-(p-fluorophenyl)-3-hydroxy-1-propyne (0.45 g) in dioxane (2 ml) and a solution of cupric sulfate pentahydrate (30 mg) in water (1 ml) under ice-cooling. The resulting mixture was heated at 80° C for 4 hours and, after cooling, the resulting mixture was filtered and the filtrate was concentrated under reduced pressure and extracted with chloroform. The chloroform extracts were dried over magnesium sulfate. After evaporation of the solvent, the residual oil was chromatographed on silica gel to afford 1-[4-(p-fluorophenyl)-4-hydroxy-2-butynyl]-4-(2-keto-1-benzimidazolinyl)piperidine as oily substance. νOHneat or νNHneat 3200 cm-1, νC=Oneat 1680 cm-1. after cooling the resulting mixture was filtered the filtrate was concentrated under reduced pressure extracted with chloroform The chloroform extracts were dried over magnesium sulfate After evaporation of the solvent the residual oil was chromatographed on silica gel

反応条件: temp:0.00; pressure:0.00; stir: