tert-butyl N-[2-(3-bromophenyl)ethyl]carbamate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of N-tert-butoxycarbonyl-3-bromophenethylamine (1.7 g) and N-methyl-N-methyloxy-2-amino-5-chloro-benzamide (1.9 g) in tetrahydrofuran (50 ml) was cooled to -70° C. To the solution was added dropwise, while stirring, a hexane solution of n-butyl lithium (1.6 mol/L) (18 ml). To the reaction mixture were added water (100 ml) and ethyl acetate (80 ml). The mixture was shaken. The organic layer was separated, which was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-amino-3′-(2-tert-butoxycarbonylaminoethyl)-5-chloro-benzophenone (1.5 g) as a yellow crystalline product. m.p.: 128-129° C. To the solution was added dropwise The mixture was shaken The organic layer was separated which was washed with water dried over anhydrous sodium sulfate The solvent was distilled off the residue was purified by means of a silica gel column chromatography

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

実験手順: A solution of N-tert-butoxycarbonyl-3-bromophenethylamine (1.7 g) and N-methyl-N-methyloxy-2-amino-5-chloro-benzamide (1.9 g) in tetrahydrofuran (50 ml) was cooled to -70° C. To the solution was added dropwise, while stirring, a hexane solution of n-butyl lithium (1.6 mol/L) (18 ml). To the reaction mixture were added water (100 ml) and ethyl acetate (80 ml). The mixture was shaken. The organic layer was separated, which was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-amino-3′-(2-tert-butoxycarbonylaminoethyl)-5-chloro-benzophenone (1.5 g) as a yellow crystalline product. m.p.: 128-129° C. To the solution was added dropwise The mixture was shaken The organic layer was separated which was washed with water dried over anhydrous sodium sulfate The solvent was distilled off the residue was purified by means of a silica gel column chromatography

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

実験手順: A tetrahydrofuran (70 ml) solution of N-methyl-N-methyloxy-2-amino-5-chlorobenzamide (6.4 g) and N-tert-butoxycarbonyl-3-bromophenethylamine (6.0 g) was cooled to −78° C., to which was gradually added dropwise a hexane solution of n-butyl lithium (1.6 mol/L) (67 ml). To the mixture were then added water (300 ml) and acetic acid ethyl ester (300 ml). The organic layer was washed with water and dried over anhydrous MgSO4, and the solvent was distilled off. The residual oily compound was purified by means of a silica gel column chromatography, followed by recrystallization from hexane to afford 2-amino-4′-(2-tert-butoxycarbonylaminoethyl)-5-chlorobenzophenone (3.97 g) as a pale yellow crystalline product. The organic layer was washed with water dried over anhydrous MgSO4 the solvent was distilled off The residual oily compound was purified by means of a silica gel column chromatography followed by recrystallization from hexane

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

実験手順: A tetrahydrofuran (70 ml) solution of N-methyl-N-methyloxy-2-amino-5-chlorobenzamide (6.4 g) and N-tert-butoxycarbonyl-3-bromophenethylamine (6.0 g) was cooled to −78° C., to which was gradually added dropwise a hexane solution of n-butyl lithium (1.6 mol/L) (67 ml). To the mixture were then added water (300 ml) and acetic acid ethyl ester (300 ml). The organic layer was washed with water and dried over anhydrous MgSO4, and the solvent was distilled off. The residual oily compound was purified by means of a silica gel column chromatography, followed by recrystallization from hexane to afford 2-amino-4′-(2-tert-butoxycarbonylaminoethyl)-5-chlorobenzophenone (3.97 g) as a pale yellow crystalline product. The organic layer was washed with water dried over anhydrous MgSO4 the solvent was distilled off The residual oily compound was purified by means of a silica gel column chromatography followed by recrystallization from hexane

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

実験手順: A solution of N-tert-butoxycarbonyl-3-bromophenethylamine (1.7 g) and N-methyl-N-methyloxy-2-amino-5-chloro-benzamide (1.9 g) in tetrahydrofuran (50 ml) was cooled to -70° C. To the solution was added dropwise, while stirring, a hexane solution of n-butyl lithium (1.6 mol/L) (18 ml). To the reaction mixture were added water (100 ml) and ethyl acetate (80 ml). The mixture was shaken. The organic layer was separated, which was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-amino-3′-(2-tert-butoxycarbonylaminoethyl)-5-chloro-benzophenone (1.5 g) as a yellow crystalline product. m.p.: 128-129° C. To the solution was added dropwise The mixture was shaken The organic layer was separated which was washed with water dried over anhydrous sodium sulfate The solvent was distilled off the residue was purified by means of a silica gel column chromatography

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

実験手順: A tetrahydrofuran (70 ml) solution of N-methyl-N-methyloxy-2-amino-5-chlorobenzamide (6.4 g) and N-tert-butoxycarbonyl-3-bromophenethylamine (6.0 g) was cooled to −78° C., to which was gradually added dropwise a hexane solution of n-butyl lithium (1.6 mol/L) (67 ml). To the mixture were then added water (300 ml) and acetic acid ethyl ester (300 ml). The organic layer was washed with water and dried over anhydrous MgSO4, and the solvent was distilled off. The residual oily compound was purified by means of a silica gel column chromatography, followed by recrystallization from hexane to afford 2-amino-4′-(2-tert-butoxycarbonylaminoethyl)-5-chlorobenzophenone (3.97 g) as a pale yellow crystalline product. The organic layer was washed with water dried over anhydrous MgSO4 the solvent was distilled off The residual oily compound was purified by means of a silica gel column chromatography followed by recrystallization from hexane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butyl [2-(3-bromophenyl)ethyl]carbamate (0.60 g, 1.99 mmol) was dissolved in dry DMF (18 mL) in a under nitrogen atmosphere. Zinc cyanide (0.47 g, 3.99 mmol) and tetrakis(triphenylphosphine)palladium (0.18 g, 0.16 mmol) was added. The reaction mixture was heated in a microwave reactor at 150° C. for 20 mins. The procedure was repeated two more times with equal amount of starting material and the resulting three mixtures were combined and diluted with EtOAc. The mixture was washed with saturated aqueous NaHCO3 and water, dried with Na2SO4, filtered and evaporated. The crude product was purified using Biotage Horizon HPFC system using Heptane and EtOAc as eluant affording the title compound (0.95 g, 64.3%). 1H NMR (500 MHz, CDCl3): δ 1.39 (s, 9H), 2.82 (t, 2H), 3.34 (q, 2H), 4.75 (bs, 1H), 7.37-7.50 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 28.57, 36.09, 41.63, 79.61, 112.69, 119.05, 129.56, 130.38, 132.57, 133.68, 140.86, 156.06. The mixture was washed with saturated aqueous NaHCO3 and water dried with Na2SO4 filtered evaporated The crude product was purified

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butyl [2-(3-bromophenyl)ethyl]carbamate (0.60 g, 1.99 mmol) was dissolved in dry DMF (18 mL) in a under nitrogen atmosphere. Zinc cyanide (0.47 g, 3.99 mmol) and tetrakis(triphenylphosphine)palladium (0.18 g, 0.16 mmol) was added. The reaction mixture was heated in a microwave reactor at 150° C. for 20 mins. The procedure was repeated two more times with equal amount of starting material and the resulting three mixtures were combined and diluted with EtOAc. The mixture was washed with saturated aqueous NaHCO3 and water, dried with Na2SO4, filtered and evaporated. The crude product was purified using Biotage Horizon HPFC system using Heptane and EtOAc as eluant affording the title compound (0.95 g, 64.3%). 1H NMR (500 MHz, CDCl3): δ 1.39 (s, 9H), 2.82 (t, 2H), 3.34 (q, 2H), 4.75 (bs, 1H), 7.37-7.50 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 28.57, 36.09, 41.63, 79.61, 112.69, 119.05, 129.56, 130.38, 132.57, 133.68, 140.86, 156.06. The mixture was washed with saturated aqueous NaHCO3 and water dried with Na2SO4 filtered evaporated The crude product was purified

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

実験手順: A solution of N-tert-butoxycarbonyl-3-bromophenethylamine (1.7 g) and N-methyl-N-methyloxy-2-amino-5-chloro-benzamide (1.9 g) in tetrahydrofuran (50 ml) was cooled to -70° C. To the solution was added dropwise, while stirring, a hexane solution of n-butyl lithium (1.6 mol/L) (18 ml). To the reaction mixture were added water (100 ml) and ethyl acetate (80 ml). The mixture was shaken. The organic layer was separated, which was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-amino-3′-(2-tert-butoxycarbonylaminoethyl)-5-chloro-benzophenone (1.5 g) as a yellow crystalline product. m.p.: 128-129° C. To the solution was added dropwise The mixture was shaken The organic layer was separated which was washed with water dried over anhydrous sodium sulfate The solvent was distilled off the residue was purified by means of a silica gel column chromatography

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

実験手順: A tetrahydrofuran (70 ml) solution of N-methyl-N-methyloxy-2-amino-5-chlorobenzamide (6.4 g) and N-tert-butoxycarbonyl-3-bromophenethylamine (6.0 g) was cooled to −78° C., to which was gradually added dropwise a hexane solution of n-butyl lithium (1.6 mol/L) (67 ml). To the mixture were then added water (300 ml) and acetic acid ethyl ester (300 ml). The organic layer was washed with water and dried over anhydrous MgSO4, and the solvent was distilled off. The residual oily compound was purified by means of a silica gel column chromatography, followed by recrystallization from hexane to afford 2-amino-4′-(2-tert-butoxycarbonylaminoethyl)-5-chlorobenzophenone (3.97 g) as a pale yellow crystalline product. The organic layer was washed with water dried over anhydrous MgSO4 the solvent was distilled off The residual oily compound was purified by means of a silica gel column chromatography followed by recrystallization from hexane