1-phenylbut-3-yn-1-amine

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 187 mg of 1-phenylbut-3-yn-1-amine (Formula 17) in 5 mL of dichloromethane was added 0.16 mL of 2-chloroethyl isocyanate and 0.26 mL of triethylamine. The mixture was stirred at room temperature for 2 hours. Then, dichloromethane was removed. Column chromatography (3% methanol/dichloromethane) followed by recrystallization from chloroform to give 25 mg of 1-(2-chloroethyl)-3-(1-phenylbut-3-ynyl)urea (Formula 18) as a white solid and 200 mg of impure material which was used without further purification. 1H NMR (300 MHz, CDCl3) δ 2.02-2.04 (m, 1H), 2.64-2.82 (m, 2H), 3.49-3.61 (m, 4H), 4.80 (br, 1H), 4.92-5.05 (m, 2H), 7.26-7.37 (m, 5H) Then, dichloromethane was removed Column chromatography (3% methanol/dichloromethane) followed by recrystallization from chloroform

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

Procedure: To a solution of 187 mg of 1-phenylbut-3-yn-1-amine (Formula 17) in 5 mL of dichloromethane was added 0.16 mL of 2-chloroethyl isocyanate and 0.26 mL of triethylamine. The mixture was stirred at room temperature for 2 hours. Then, dichloromethane was removed. Column chromatography (3% methanol/dichloromethane) followed by recrystallization from chloroform to give 25 mg of 1-(2-chloroethyl)-3-(1-phenylbut-3-ynyl)urea (Formula 18) as a white solid and 200 mg of impure material which was used without further purification. 1H NMR (300 MHz, CDCl3) δ 2.02-2.04 (m, 1H), 2.64-2.82 (m, 2H), 3.49-3.61 (m, 4H), 4.80 (br, 1H), 4.92-5.05 (m, 2H), 7.26-7.37 (m, 5H) Then, dichloromethane was removed Column chromatography (3% methanol/dichloromethane) followed by recrystallization from chloroform

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

Procedure: To a solution of 1.03 g of tert-butyl 1-phenylbut-3-ynylcarbamate (Formula 16) in 15 mL of dichloromethane was added 3 mL of trifluoroacetic acid. The mixture was stirred at room temperature for 1 hour. Then, dichloromethane was removed. The residue was diluted with water and extracted with ethyl acetate. Combined ethyl acetate was washed with brine, dried over sodium sulfate and concentrated. Column chromatography (60% ethyl acetate/hexane) gave 564 mg (93%) of 1-phenylbut-3-yn-1-amine (Formula 17) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 2.04-2.05 (m, 1H), 2.43-2.63 (m, 2H), 4.14-4.19 (m, 1H), 7.24-7.40 (m, 5H). Then, dichloromethane was removed The residue was diluted with water extracted with ethyl acetate Combined ethyl acetate was washed with brine dried over sodium sulfate concentrated

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

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

Procedure: Dissolve (RS)-1-amino-1-phenyl-but-3-yne [Zh. Org. Khim. 18(4), 980-983 (1982) A. Mostamandi, L. A. Remizova, A. L. Pavienkova, I. A. Favorskaya] (20.0 g, 138 mmol) and (-)-5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide (35.0 g, 129 mmol) in refluxing ethanol (300 mL). Cool the solution to ambient temperature and collect the precipitate by filtration. Rinse the precipitate with a small amount of isopropanol/ethanol (1/1). Two recrystallizations from ethanol gives (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g). Combine (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g, 50.4 mmol) with a mixture of aqueous 1M potassium hydroxide solution (100 mL) and toluene (50 mL) and stir for 0.75 hour. Separate the layers and extract the aqueous layer with toluene (50 mL), combine the organic layers, dry over (Na2SO4), and filter to obtain a solution. Pass hydrogen chloride gas through the solution until it is saturated and then remove the precipitate by filtration and rinse with toluene. Recrystallize from butanone (120 mL) to give 7.0 g the title compound. Specific rotation [α]2D0 =11.0° (c=0.500, MeOH). collect the precipitate by filtration Rinse the precipitate with a small amount of isopropanol/ethanol (1/1) Two recrystallizations from ethanol

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

Procedure: Dissolve (RS)-1-amino-1-phenyl-but-3-yne [Zh. Org. Khim. 18(4), 980-983 (1982) A. Mostamandi, L. A. Remizova, A. L. Pavienkova, I. A. Favorskaya] (20.0 g, 138 mmol) and (-)-5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide (35.0 g, 129 mmol) in refluxing ethanol (300 mL). Cool the solution to ambient temperature and collect the precipitate by filtration. Rinse the precipitate with a small amount of isopropanol/ethanol (1/1). Two recrystallizations from ethanol gives (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g). Combine (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g, 50.4 mmol) with a mixture of aqueous 1M potassium hydroxide solution (100 mL) and toluene (50 mL) and stir for 0.75 hour. Separate the layers and extract the aqueous layer with toluene (50 mL), combine the organic layers, dry over (Na2SO4), and filter to obtain a solution. Pass hydrogen chloride gas through the solution until it is saturated and then remove the precipitate by filtration and rinse with toluene. Recrystallize from butanone (120 mL) to give 7.0 g the title compound. Specific rotation [α]2D0 =11.0° (c=0.500, MeOH). collect the precipitate by filtration Rinse the precipitate with a small amount of isopropanol/ethanol (1/1) Two recrystallizations from ethanol

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

Procedure: Dissolve (RS)-1-amino-1-phenyl-but-3-yne [Zh. Org. Khim. 18(4), 980-983 (1982) A. Mostamandi, L. A. Remizova, A. L. Pavienkova, I. A. Favorskaya] (20.0 g, 138 mmol) and (-)-5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide (35.0 g, 129 mmol) in refluxing ethanol (300 mL). Cool the solution to ambient temperature and collect the precipitate by filtration. Rinse the precipitate with a small amount of isopropanol/ethanol (1/1). Two recrystallizations from ethanol gives (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g). Combine (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g, 50.4 mmol) with a mixture of aqueous 1M potassium hydroxide solution (100 mL) and toluene (50 mL) and stir for 0.75 hour. Separate the layers and extract the aqueous layer with toluene (50 mL), combine the organic layers, dry over (Na2SO4), and filter to obtain a solution. Pass hydrogen chloride gas through the solution until it is saturated and then remove the precipitate by filtration and rinse with toluene. Recrystallize from butanone (120 mL) to give 7.0 g the title compound. Specific rotation [α]2D0 =11.0° (c=0.500, MeOH). collect the precipitate by filtration Rinse the precipitate with a small amount of isopropanol/ethanol (1/1) Two recrystallizations from ethanol

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

Procedure: Dissolve (RS)-1-amino-1-phenyl-but-3-yne [Zh. Org. Khim. 18(4), 980-983 (1982) A. Mostamandi, L. A. Remizova, A. L. Pavienkova, I. A. Favorskayal] (20.0 g, 138 mmol) and (-)-5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2,-dioxaphosphorinane 2-oxide (35.0 g, 129 mmol) in refluxing ethanol (300 mL). Cool the solution to ambient temperature and collect the precipitate by filtration. Rinse the precipitate with a small amount of isopropanol/ethanol (1/1). Two recrystallizations from ethanol gives (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g). Combine (R)-1-amino-1-phenyl-but-3-yne 5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-1,3,2-dioxaphosphorinane 2-oxide salt (21 g, 50.4 mmol) with a mixture of aqueous 1M potassium hydroxide solution (100 mL) and toluene (50 mL) and stir or 0.75 hour. Separate the layers and extract the aqueous layer with toluene (50 mL), combine the organic layers, dry over (Na2SO4), and filter to obtain a solution. Pass hydrogen chloride gas through the solution until it is saturated and then remove the precipitate by filtration and rinse with toluene. Recrystallize from butanone (120 mL) to give 7.0 g the title compound. Specific rotation [α]2D0 =11.0° (c=0.500, MeOH). collect the precipitate by filtration Rinse the precipitate with a small amount of isopropanol/ethanol (1/1) Two recrystallizations from ethanol

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

Procedure: To a solution of 187 mg of 1-phenylbut-3-yn-1-amine (Formula 17) in 5 mL of dichloromethane was added 0.16 mL of 2-chloroethyl isocyanate and 0.26 mL of triethylamine. The mixture was stirred at room temperature for 2 hours. Then, dichloromethane was removed. Column chromatography (3% methanol/dichloromethane) followed by recrystallization from chloroform to give 25 mg of 1-(2-chloroethyl)-3-(1-phenylbut-3-ynyl)urea (Formula 18) as a white solid and 200 mg of impure material which was used without further purification. 1H NMR (300 MHz, CDCl3) δ 2.02-2.04 (m, 1H), 2.64-2.82 (m, 2H), 3.49-3.61 (m, 4H), 4.80 (br, 1H), 4.92-5.05 (m, 2H), 7.26-7.37 (m, 5H) Then, dichloromethane was removed Column chromatography (3% methanol/dichloromethane) followed by recrystallization from chloroform

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

Procedure: To a solution of 1.03 g of tert-butyl 1-phenylbut-3-ynylcarbamate (Formula 16) in 15 mL of dichloromethane was added 3 mL of trifluoroacetic acid. The mixture was stirred at room temperature for 1 hour. Then, dichloromethane was removed. The residue was diluted with water and extracted with ethyl acetate. Combined ethyl acetate was washed with brine, dried over sodium sulfate and concentrated. Column chromatography (60% ethyl acetate/hexane) gave 564 mg (93%) of 1-phenylbut-3-yn-1-amine (Formula 17) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 2.04-2.05 (m, 1H), 2.43-2.63 (m, 2H), 4.14-4.19 (m, 1H), 7.24-7.40 (m, 5H). Then, dichloromethane was removed The residue was diluted with water extracted with ethyl acetate Combined ethyl acetate was washed with brine dried over sodium sulfate concentrated

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