1,3-二-(Boc-氨基)-2-羟基丙烷

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of dimethyl sulfoxide (25.2 ml, 0.36 mol) in methylene chloride (357 ml) at −78° C. (dry ice/acetone) was added a solution of oxalyl chloride (20 ml, 0.23 mol) in methylene chloride (115 ml). The reaction mixture was stirred at −78° C. for 30 min under an atmosphere of N2 then a solution of (3-tert-Butoxycarbonylamino-2-hydroxy-propyl)-carbamic acid tert-butyl ester (31.9 g, 0.11 mol) in methylene chloride (300 ml) and triethylamine (75 ml, 0.54 mol) were added. The reaction was stirred for 16 hours, allowing the reaction to warm up to room temperature. The mixture was diluted with water (800 ml) and extracted with methylene chloride (2×300 ml). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a yellowish oil. Purification via column chromatography on silica gel (ethyl acetate:hexane, 3:7, v/v) afforded the product as a white solid (28 g, 88%). 1H NMR (CDCl3) δ 1.44 (s, 18H), 4.04 (m, 4H), 5.19 (s, 1H). The reaction was stirred for 16 hours the reaction to warm up to room temperature extracted with methylene chloride (2×300 ml) The combined organic extracts were dried (Na2SO4) filtered concentrated in vacuo to afford a yellowish oil Purification via column chromatography on silica gel (ethyl acetate:hexane, 3:7, v/v)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of dimethyl sulfoxide (25.2 ml, 0.36 mol) in methylene chloride (357 ml) at −78° C. (dry ice/acetone) was added a solution of oxalyl chloride (20 ml, 0.23 mol) in methylene chloride (115 ml). The reaction mixture was stirred at −78° C. for 30 min under an atmosphere of N2 then a solution of (3-tert-Butoxycarbonylamino-2-hydroxy-propyl)-carbamic acid tert-butyl ester (31.9 g, 0.11 mol) in methylene chloride (300 ml) and triethylamine (75 ml, 0.54 mol) were added. The reaction was stirred for 16 hours, allowing the reaction to warm up to room temperature. The mixture was diluted with water (800 ml) and extracted with methylene chloride (2×300 ml). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a yellowish oil. Purification via column chromatography on silica gel (ethyl acetate:hexane, 3:7, v/v) afforded the product as a white solid (28 g, 88%). 1H NMR (CDCl3) δ 1.44 (s, 18H), 4.04 (m, 4H), 5.19 (s, 1H). The reaction was stirred for 16 hours the reaction to warm up to room temperature extracted with methylene chloride (2×300 ml) The combined organic extracts were dried (Na2SO4) filtered concentrated in vacuo to afford a yellowish oil Purification via column chromatography on silica gel (ethyl acetate:hexane, 3:7, v/v)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of dimethyl sulfoxide (25.2 ml, 0.36 mol) in methylene chloride (357 ml) at −78° C. (dry ice/acetone) was added a solution of oxalyl chloride (20 ml, 0.23 mol) in methylene chloride (115 ml). The reaction mixture was stirred at −78° C. for 30 min under an atmosphere of N2 then a solution of (3-tert-Butoxycarbonylamino-2-hydroxy-propyl)-carbamic acid tert-butyl ester (31.9 g, 0.11 mol) in methylene chloride (300 ml) and triethylamine (75 ml, 0.54 mol) were added. The reaction was stirred for 16 hours, allowing the reaction to warm up to room temperature. The mixture was diluted with water (800 ml) and extracted with methylene chloride (2×300 ml). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a yellowish oil. Purification via column chromatography on silica gel (ethyl acetate:hexane, 3:7, v/v) afforded the product as a white solid (28 g, 88%). 1H NMR (CDCl3) δ 1.44 (s, 18H), 4.04 (m, 4H), 5.19 (s, 1H). The reaction was stirred for 16 hours the reaction to warm up to room temperature extracted with methylene chloride (2×300 ml) The combined organic extracts were dried (Na2SO4) filtered concentrated in vacuo to afford a yellowish oil Purification via column chromatography on silica gel (ethyl acetate:hexane, 3:7, v/v)

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

实验步骤: To a solution of N,N′-di-Boc-2-hydroxy-1,3-diaminopropane (13.19 g, 45.4 mmol) and triethylamine (1.5 eq, 9.5 ml, 68.1 mmol) in dry 50 ml CH2Cl2 was added dropwise a solution of methanesulfonyl chloride (1.5 eq, 5.25 ml, 68 mmol) in dry 15 ml CH2Cl2 over a period of 1 h at 0° C. with stirring under nitrogen. After the addition, the reaction was stirred overnight at room temperature. Water was slowly added to quench the reaction; the organic layer was separated and then washed with water (5×15 ml) and dried over Na2SO4 and evaporated to give white solid. Recrystallization from hot acetone and cyclohexane gave 10.36 g (62%) white solid. M.p.=127° C. After the addition the reaction was stirred overnight at room temperature to quench the reaction the organic layer was separated washed with water (5×15 ml) dried over Na2SO4 evaporated to give white solid Recrystallization from hot acetone and cyclohexane

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

实验步骤: 1,3-di(tert-butyloxycarbonylamino)propan-2-ol (example 10a) (2.89 g, 10 mmol) and triethylamine (2.22 ml, 16 mmol) were dissolved in anhydrous dichloromethane (100 ml). The reaction mixture was cooled in an ice bath followed by dropwise addition of tosyl chloride (2.272 g, 12 mmol) dissolved in dichloromethane (30 ml). The reaction mixture was then stirred at room temperature for 72 hours. One equivalent of chloride and 1.6 of triethylamine were added after 48 hours. Water was added to stop the reaction and the medium was allowed to settle. The organic phase was washed several times with water. The aqueous phases were combined and extracted again with dichloromethane. The organic phase was dried on magnesium sulfate, filtered and the solvent was evaporated. The residue obtained (6.44 g) was purified by chromatography on silica gel (eluent:dichloromethane followed by dichloromethane/methanol 99:1) to yield the desired compound as a white solid. The reaction mixture was cooled in an ice bath the reaction The organic phase was washed several times with water extracted again with dichloromethane The organic phase was dried on magnesium sulfate filtered the solvent was evaporated The residue obtained (6.44 g) was purified by chromatography on silica gel (eluent:dichloromethane followed by dichloromethane/methanol 99:1)

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

实验步骤: To 29.0 g (0.1 mol) of di-tert-butyl 2-hydroxypropane-1,3-diyldicarbamate and 17.0 g (0.25 mol) of imidazole in 200 ml DMF at 0° C., was added 18.09 g (0.12 mol) of t-butyldimethylsilylchloride (TBDSMCl) in portions. The reaction was warmed up to RT and stirred for 2 hours. To this mixture was added 400 ml ether and 400 ml brine. The layers were separated and the aqueous layer was extracted with 400 ml ether. The combined organic layer was dried and concentrated to give 35 g of di-tert-butyl 2-(tert-butyldimethylsilyloxy)propane-1,3-diyldicarbamate (86% yield). The layers were separated the aqueous layer was extracted with 400 ml ether The combined organic layer was dried concentrated

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

实验步骤: To 29.0 g (0.1 mol) of di-tert-butyl 2-hydroxypropane-1,3-diyldicarbamate and 17.0 g (0.25 mol) of imidazole in 200 ml DMF at 0° C., was added 18.09 g (0.12 mol) of t-butyldimethylsilylchloride (TBDSMCl) in portions. The reaction was warmed up to RT and stirred for 2 hours. To this mixture was added 400 ml ether and 400 ml brine. The layers were separated and the aqueous layer was extracted with 400 ml ether. The combined organic layer was dried and concentrated to give 35 g of di-tert-butyl 2-(tert-butyldimethylsilyloxy)propane-1,3-diyldicarbamate (86% yield). The layers were separated the aqueous layer was extracted with 400 ml ether The combined organic layer was dried concentrated

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

实验步骤: 2-Nitro-5-fluorophenol (8.4 g) and (3-tert-butoxycarbonylamino-2-hydroxy-propyl)-carbamic acid tert-butyl ester (17.0 g) were dissolved in THF (60 ml) and triphenylphosphine (21 g) and di-tert-butyl-azodicarboxylate (18.4 g) were added. The exothermic reaction was cooled in an ice bath. Then the mixture was stirred at room temperature overnight. It was concentrated in vacuo and the residue was dissolved in dichloromethane, washed with water and 1M NaOH. The organic layer was dried and concentrated in vacuo. The residue was purified by chromatography (silica/dichloromethane:methanol 25:1). The exothermic reaction was cooled in an ice bath It was concentrated in vacuo the residue was dissolved in dichloromethane washed with water and 1M NaOH The organic layer was dried concentrated in vacuo The residue was purified by chromatography (silica/dichloromethane:methanol 25:1)

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

实验步骤: 2-Nitro-5-fluorophenol (8.4 g) and (3-tert-butoxycarbonylamino-2-hydroxy-propyl)-carbamic acid tert-butyl ester (17.0 g) were dissolved in THF (60 ml) and triphenylphosphine (21 g) and di-tert-butyl-azodicarboxylate (18.4 g) were added. The exothermic reaction was cooled in an ice bath. Then the mixture was stirred at room temperature overnight. It was concentrated in vacuo and the residue was dissolved in dichloromethane, washed with water and 1M NaOH. The organic layer was dried and concentrated in vacuo. The residue was purified by chromatography (silica/dichloromethane:methanol 25:1). The exothermic reaction was cooled in an ice bath It was concentrated in vacuo the residue was dissolved in dichloromethane washed with water and 1M NaOH The organic layer was dried concentrated in vacuo The residue was purified by chromatography (silica/dichloromethane:methanol 25:1)

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

实验步骤: To 29.0 g (0.1 mol) of di-tert-butyl 2-hydroxypropane-1,3-diyldicarbamate and 17.0 g (0.25 mol) of imidazole in 200 ml DMF at 0° C., was added 18.09 g (0.12 mol) of t-butyldimethylsilylchloride (TBDSMCl) in portions. The reaction was warmed up to RT and stirred for 2 hours. To this mixture was added 400 ml ether and 400 ml brine. The layers were separated and the aqueous layer was extracted with 400 ml ether. The combined organic layer was dried and concentrated to give 35 g of di-tert-butyl 2-(tert-butyldimethylsilyloxy)propane-1,3-diyldicarbamate (86% yield). The layers were separated the aqueous layer was extracted with 400 ml ether The combined organic layer was dried concentrated

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

实验步骤: To a solution of di-tert-butyl (2-hydroxy-1,3-propanediyl)biscarbamate (200 g) in methylene chloride (1.2 L) was added triethylamine (384 ml) under cooling on an ice-water bath and then a solution of methanesulfonyl chloride (64 ml) in methylene chloride (300 ml) was dropwise added at a temperature below 15° C. The mixture was stirred at the same temperature for 1.5 hours and quenched with saturated aqueous sodium hydrogencarbonate solution (200 ml). The organic layer was made acidic (pH=3) with diluted hydrochloric acid, and washed with saturated aqueous sodium hydrogencarbonate solution and brine, and dried over anhydrous magnesium sulfate. Concentration under reduced pressure gave a residue, which was triturated with ethyl acetate (100 ml)—hexane (500 ml) to give 2-[(tert-butoxycarbonyl)amino]-1-{[(tert-butoxycarbonyl)amino]methyl}ethyl methanesulfonate (202 g) as a white solid. under cooling on an ice-water bath quenched with saturated aqueous sodium hydrogencarbonate solution (200 ml) washed with saturated aqueous sodium hydrogencarbonate solution and brine dried over anhydrous magnesium sulfate Concentration under reduced pressure gave a residue, which was triturated with ethyl acetate (100 ml)—hexane (500 ml)

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

实验步骤: To a solution of di-tert-butyl (2-hydroxy-1,3-propanediyl)biscarbamate (200 g) in methylene chloride (1.2 L) was added triethylamine (384 ml) under cooling on an ice-water bath and then a solution of methanesulfonyl chloride (64 ml) in methylene chloride (300 ml) was dropwise added at a temperature below 15° C. The mixture was stirred at the same temperature for 1.5 hours and quenched with saturated aqueous sodium hydrogencarbonate solution (200 ml). The organic layer was made acidic (pH=3) with diluted hydrochloric acid, and washed with saturated aqueous sodium hydrogencarbonate solution and brine, and dried over anhydrous magnesium sulfate. Concentration under reduced pressure gave a residue, which was triturated with ethyl acetate (100 ml)—hexane (500 ml) to give 2-[(tert-butoxycarbonyl)amino]-1-{[(tert-butoxycarbonyl)amino]methyl}ethyl methanesulfonate (202 g) as a white solid. under cooling on an ice-water bath quenched with saturated aqueous sodium hydrogencarbonate solution (200 ml) washed with saturated aqueous sodium hydrogencarbonate solution and brine dried over anhydrous magnesium sulfate Concentration under reduced pressure gave a residue, which was triturated with ethyl acetate (100 ml)—hexane (500 ml)