(E)-1,3-dichloroprop-1-ene

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (72.5 g), Tetrabutyl ammonium bromide (30 g) and de-ionized water (75 mL) were added to (R)-1-(1-naphthyl)ethylamine (150 g) in toluene (750 mL) at room temperature. The reaction mixture was heated to 60° C. to 70° C. and added trans 1,3-dichloropropene (126.4 g). The reaction mass was refluxed for 3 hours at 90° C. to 95° C. The reaction mixture was cooled to 40° C., and washed with de-ionized water (2×450 mL). The organic layer was separated and concentrated under vacuum at 55° C. to 60° C. to give an oily residue. The residue was dissolved in acetone (750 mL), added de-ionized water (150 ml) and the pH of the reaction mixture was adjusted to 1-2 using aqueous hydrochloric acid (6 Normal; 150 mL). The solid was stirred at 30° C. to 40° C. for 30 min, cooled to 20° C. to 25° C. and stirred for 1 hour. The resulting solid was filtered and suspended in acetone (300 mL), the suspensions were filtered and washed with acetone (150 mL). The resulting solid was suspended in de-ionized water (300 mL), filtered and washed with de-ionized water (225 mL). The resulting wet solid was suspended in a mixture of toluene (750 mL), methanol (375 mL) and de-ionized water (375 mL). The pH of the mixture was adjusted to 11-11.5 using aqueous sodium hydroxide solution (20%; 150 mL) and stirred for 30 minutes. The layers were separated and organic layer was washed with de-ionized water (2×300 mL). The organic layer was concentrated under reduced pressure to give 3-chloro-N-[(1R)-1-(naphthalen-1-yl)ethyl]prop-2-en-1-amine as an oil. The reaction mixture was heated to 60° C. to 70° C. The reaction mass was refluxed for 3 hours at 90° C. to 95° C washed with de-ionized water (2×450 mL) The organic layer was separated concentrated under vacuum at 55° C. to 60° C. to give an oily residue cooled to 20° C. to 25° C. stirred for 1 hour The resulting solid was filtered the suspensions were filtered washed with acetone (150 mL) filtered washed with de-ionized water (225 mL) The resulting wet solid was suspended in a mixture of toluene (750 mL), methanol (375 mL) and de-ionized water (375 mL) stirred for 30 minutes The layers were separated organic layer was washed with de-ionized water (2×300 mL) The organic layer was concentrated under reduced pressure

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

Procedure: A mixture of 6-hydroxy-2-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)-4-methylpyridine (0.9 g, 3.3 mmol) and NaH (60 % in oil, 0.16 g, 4 mmol) in acetonitrile (20 ml) and DMF (1 ml) is stirred for 10 min at ambient temperature and (E)-1,3-dichloropropene (0.4 g, 3.6 mmol) is added. After stirring for 60 h at ambient temperature, the remaining NaH is deactivated and the resulting mixture is diluted with pentane/ethyl acetate (by volume ration 1/1) and filtered through a bed of silica gel. The filtrate is washed with water. The organic layer is dried with anhydrous magnesium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v) yields the title compound (0.6 g, 52 % yield) as an colorless oil. After stirring for 60 h at ambient temperature filtered through a bed of silica gel The filtrate is washed with water The organic layer is dried with anhydrous magnesium sulfate filtered evaporated in vacuo Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v)

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

Procedure: Method B, reacting 2-(nitromethylene)imidazolidine with trans-1,3-dichloro-1-propene. Melting point: 134°-135°C.

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

Procedure: Method B, reacting 2-(nitromethylene)imidazolidine with trans-1,3-dichloro-1-propene. Melting point: 134°-135°C.

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

Procedure: Method B, reacting 2-(nitromethylene)imidazolidine with trans-1,3-dichloro-1-propene. Melting point: 134°-135°C.

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

Procedure: Method B, reacting 2-(nitromethylene)imidazolidine with trans-1,3-dichloro-1-propene. Melting point: 134°-135°C.

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (72.5 g), Tetrabutyl ammonium bromide (30 g) and de-ionized water (75 mL) were added to (R)-1-(1-naphthyl)ethylamine (150 g) in toluene (750 mL) at room temperature. The reaction mixture was heated to 60° C. to 70° C. and added trans 1,3-dichloropropene (126.4 g). The reaction mass was refluxed for 3 hours at 90° C. to 95° C. The reaction mixture was cooled to 40° C., and washed with de-ionized water (2×450 mL). The organic layer was separated and concentrated under vacuum at 55° C. to 60° C. to give an oily residue. The residue was dissolved in acetone (750 mL), added de-ionized water (150 ml) and the pH of the reaction mixture was adjusted to 1-2 using aqueous hydrochloric acid (6 Normal; 150 mL). The solid was stirred at 30° C. to 40° C. for 30 min, cooled to 20° C. to 25° C. and stirred for 1 hour. The resulting solid was filtered and suspended in acetone (300 mL), the suspensions were filtered and washed with acetone (150 mL). The resulting solid was suspended in de-ionized water (300 mL), filtered and washed with de-ionized water (225 mL). The resulting wet solid was suspended in a mixture of toluene (750 mL), methanol (375 mL) and de-ionized water (375 mL). The pH of the mixture was adjusted to 11-11.5 using aqueous sodium hydroxide solution (20%; 150 mL) and stirred for 30 minutes. The layers were separated and organic layer was washed with de-ionized water (2×300 mL). The organic layer was concentrated under reduced pressure to give 3-chloro-N-[(1R)-1-(naphthalen-1-yl)ethyl]prop-2-en-1-amine as an oil. The reaction mixture was heated to 60° C. to 70° C. The reaction mass was refluxed for 3 hours at 90° C. to 95° C washed with de-ionized water (2×450 mL) The organic layer was separated concentrated under vacuum at 55° C. to 60° C. to give an oily residue cooled to 20° C. to 25° C. stirred for 1 hour The resulting solid was filtered the suspensions were filtered washed with acetone (150 mL) filtered washed with de-ionized water (225 mL) The resulting wet solid was suspended in a mixture of toluene (750 mL), methanol (375 mL) and de-ionized water (375 mL) stirred for 30 minutes The layers were separated organic layer was washed with de-ionized water (2×300 mL) The organic layer was concentrated under reduced pressure

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

Procedure: A mixture of 6-hydroxy-2-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)-4-methylpyridine (0.9 g, 3.3 mmol) and NaH (60 % in oil, 0.16 g, 4 mmol) in acetonitrile (20 ml) and DMF (1 ml) is stirred for 10 min at ambient temperature and (E)-1,3-dichloropropene (0.4 g, 3.6 mmol) is added. After stirring for 60 h at ambient temperature, the remaining NaH is deactivated and the resulting mixture is diluted with pentane/ethyl acetate (by volume ration 1/1) and filtered through a bed of silica gel. The filtrate is washed with water. The organic layer is dried with anhydrous magnesium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v) yields the title compound (0.6 g, 52 % yield) as an colorless oil. After stirring for 60 h at ambient temperature filtered through a bed of silica gel The filtrate is washed with water The organic layer is dried with anhydrous magnesium sulfate filtered evaporated in vacuo Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v)

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

Procedure: A mixture of 6-hydroxy-2-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)-4-methylpyridine (0.9 g, 3.3 mmol) and NaH (60 % in oil, 0.16 g, 4 mmol) in acetonitrile (20 ml) and DMF (1 ml) is stirred for 10 min at ambient temperature and (E)-1,3-dichloropropene (0.4 g, 3.6 mmol) is added. After stirring for 60 h at ambient temperature, the remaining NaH is deactivated and the resulting mixture is diluted with pentane/ethyl acetate (by volume ration 1/1) and filtered through a bed of silica gel. The filtrate is washed with water. The organic layer is dried with anhydrous magnesium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v) yields the title compound (0.6 g, 52 % yield) as an colorless oil. After stirring for 60 h at ambient temperature filtered through a bed of silica gel The filtrate is washed with water The organic layer is dried with anhydrous magnesium sulfate filtered evaporated in vacuo Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v)

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

Procedure: A mixture of 6-hydroxy-2-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)-4-methylpyridine (0.9 g, 3.3 mmol) and NaH (60% in oil, 0.16 g, 4 mmol) in acetonitrile (20 ml) and DMF (1 ml) is stirred for 10 min at ambient temperature and (E)-1,3-dichloropropene (0.4 g, 3.6 mmol) is added. After stirring for 60 h at ambient temperature, the remaining NaH is deactivated and the resulting mixture is diluted with pentane/ethyl acetate (by volume ration 1/1) and filtered through a bed of silica gel. The filtrate is washed with water. The organic layer is dried with anhydrous magnesium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v) yields the title compound (0.6 g, 52% yield) as an colorless oil. After stirring for 60 h at ambient temperature filtered through a bed of silica gel The filtrate is washed with water The organic layer is dried with anhydrous magnesium sulfate filtered evaporated in vacuo Purification by flash chromatography (silica gel: pentane/ethyl acetate 9/1 v/v)

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

Procedure: Trifluoroacetamide (10.44 g, 92.4 mmol) is dissolved in THF (30 mL). Sodium hydride (60% weight dispersion in mineral oil, 3.1 g, 77 mmol) is then added in small portions at room temperature while regulating the temperature of the reaction with a water bath. The mixture is stirred at room temperature for 5 min., after which E-1,3-dichloropropene (4.5 mL, 49.4 mmol) is added. After 2 min., the mixture thickened, and the reaction was heated to reflux for 45 min. The mixture is then cooled to room temperature, and saturated aqueous ammonium chloride (20 mL) and water (40 mL) are added. The mixture is transferred to a separatory funnel and extracted with ether (2×400 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to obtained a colorless oil that was used for the next step. the temperature of the reaction with a water bath After 2 min. the reaction was heated to reflux for 45 min The mixture is then cooled to room temperature The mixture is transferred to a separatory funnel extracted with ether (2×400 mL) The combined organic layers were dried (MgSO4) concentrated under reduced pressure to obtained a colorless oil that

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

Procedure: Trifluoroacetamide (10.44 g, 92.4 mmol) is dissolved in THF (30 mL). Sodium hydride (60% weight dispersion in mineral oil, 3.1 g, 77 mmol) is then added in small portions at room temperature while regulating the temperature of the reaction with a water bath. The mixture is stirred at room temperature for 5 min., after which E-1,3-dichloropropene (4.5 mL, 49.4 mmol) is added. After 2 min., the mixture thickened, and the reaction was heated to reflux for 45 min. The mixture is then cooled to room temperature, and saturated aqueous ammonium chloride (20 mL) and water (40 mL) are added. The mixture is transferred to a separatory funnel and extracted with ether (2×400 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to obtained a colorless oil that was used for the next step. the temperature of the reaction with a water bath After 2 min. the reaction was heated to reflux for 45 min The mixture is then cooled to room temperature The mixture is transferred to a separatory funnel extracted with ether (2×400 mL) The combined organic layers were dried (MgSO4) concentrated under reduced pressure to obtained a colorless oil that