苄基(S)-缬氨醇

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl(S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil. extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) added to a flask The organic layer was separated concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil The reaction mixture was stirred at room temperature for 40 minutes extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl(S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil. extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) added to a flask The organic layer was separated concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil The reaction mixture was stirred at room temperature for 40 minutes extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl(S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil. extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) added to a flask The organic layer was separated concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil The reaction mixture was stirred at room temperature for 40 minutes extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl(S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil. extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) added to a flask The organic layer was separated concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil The reaction mixture was stirred at room temperature for 40 minutes extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl (S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil. extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) added to a flask The organic layer was separated concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil The reaction mixture was stirred at room temperature for 40 minutes extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (S)-2-amino-3-methylbutan-1-ol (10.0 g, 97 mmol), benzaldehyde (10.34 mL, 102 mmol), and 4-methylbenzenesulfonic acid hydrate (3.69 mg, 0.019 mmol) in benzene (300 mL) was refluxed (80° C.) for 15 h with a Dean-Stark trap (ca. 2 mL water was collected). The solution was concentrated (leaving a pale yellow solid) and redissolved in methanol (200 mL). The methanol solution was cooled in an ice bath then treated with sodium cyanotrihydroborate (7.31 g, 116 mmol). The ice bath was removed and the mixture was stirred for 30 min (50% conversion). NaBH4 (3 g, 79.3 mmol) were added and stirring continued at room temperature for 20 min. The mixture was concentrated. The remaining residue was taken up in ethyl acetate (200 mL) then washed with saturated NaHCO3 (100 mL) then brine (100 mL). The organic layer was dried (MgSO4), filtered, then concentrated to give (S)-2-(benzylamino)-3-methylbutan-1-ol as a colorless oil. This oil was dissolved in dichloromethane (300 mL). N-ethyl-N-isopropylpropan-2-amine (67.5 mL, 388 mmol) was added. The flask was flushed with nitrogen, and the mixture was cooled in a dry-ice/acetone bath. Thionyl chloride (7.78 mL, 107 mmol) was added dropwise, maintaining the internal temperature between −60° C. and −30° C. After addition was complete, the cooling bath was removed and the mixture gradually warmed to room temperature over 1 h. The mixture was concentrated. The residue was purified by silica gel flash column chromatography to give the title compound (18 g) as an orange oil (mixture of epimers). LCMS m/z=240.0 [M+H]+. with a Dean-Stark trap (ca. 2 mL water was collected) The solution was concentrated ( leaving a pale yellow solid) and The ice bath was removed stirring continued at room temperature for 20 min The mixture was concentrated then washed with saturated NaHCO3 (100 mL) The organic layer was dried (MgSO4) filtered concentrated

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl(S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil. extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) added to a flask The organic layer was separated concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil The reaction mixture was stirred at room temperature for 40 minutes extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate solution and brine dried concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)