1-O-benzyl 2-O-methyl aziridine-1,2-dicarboxylate

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

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

Procedure: To a stirred solution of (S)-1-benzyl 2-methyl aziridine-1,2-dicarboxylate (prepared according to the literature procedure: Org. Biomol. Chem., 2005, 3, 3357, 2.7 g, 11.4 mmol) in dichloromethane (30 mL), boron trifluoride etherate (0.01 mL, 0.11 mmol) was added at 0° C. followed by absolute ethanol (1.05 g, 22.9 mmol). The reaction mixture was stirred at room temperature for an hour, after which the solution was quenched with saturated bicarbonate solution (2 mL), extracted with dichloromethane (3×25 mL), organic layers were washed with water (25 mL), brine solution (25 mL) and dried over sodium sulfate. The removal of solvents afforded crude product, which was purified by silica gel column chromatography using a gradient of ethyl acetate in pet. ether. Yield: 2.0 g (63%). 1H NMR (400 MHz, DMSO-d6) δ: 1.08 (t, 3H), 3.38-3.46 (m, 2H), 3.57-3.63 (m, 2H), 3.70 (s, 3H), 4.26-4.31 (m, 1H), 5.04 (s, 2H), 7.30-7.39 (m, 5H), 7.73 (d, 1H). after which the solution was quenched with saturated bicarbonate solution (2 mL) extracted with dichloromethane (3×25 mL), organic layers were washed with water (25 mL), brine solution (25 mL) dried over sodium sulfate The removal of solvents afforded crude product, which was purified by silica gel column chromatography

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

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

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

Procedure: To a stirred solution of 1-benzyl 2-methyl (S)-(−)-1,2-aziridinedicarboxylate (1.88 g) in dichloromethane (30 ml) were added at 0° C. 1-phenyl-ethanol (9.77 g) and boron trifluoride etherate (2.0 ml). After stirring the mixture for one hour the cooling bath was removed and stirring was continued overnight. Then the reaction mixture was poured onto saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0->90:10) to give S)-2-benzyloxycarbonylamino-3-(1-phenyl-ethoxy)-propionic acid methyl ester (1.34 g, 47%) as a light yellow oil. MS (ISP): 358.2 ([M+H]+)). was removed stirring was continued overnight Then the reaction mixture was poured onto saturated sodium bicarbonate solution extracted with ethyl acetate The combined organic layers were washed with brine dried (MgSO4) concentrated The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0->90:10)

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

Procedure: To a stirred solution of 1-benzyl 2-methyl (S)-(−)-1,2-aziridinedicarboxylate (1.88 g) in dichloromethane (30 ml) were added at 0° C. 1-phenyl-ethanol (9.77 g) and boron trifluoride etherate (2.0 ml). After stirring the mixture for one hour the cooling bath was removed and stirring was continued overnight. Then the reaction mixture was poured onto saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0->90:10) to give S)-2-benzyloxycarbonylamino-3-(1-phenyl-ethoxy)-propionic acid methyl ester (1.34 g, 47%) as a light yellow oil. MS (ISP): 358.2 ([M+H]+)). was removed stirring was continued overnight Then the reaction mixture was poured onto saturated sodium bicarbonate solution extracted with ethyl acetate The combined organic layers were washed with brine dried (MgSO4) concentrated The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0->90:10)

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

Procedure: To a stirred solution of 1-benzyl 2-methyl(S)-(−)-1,2-aziridinedicarboxylate (1.88 g) in dichloromethane (30 ml) were added at 0° C. 1-phenyl-ethanol (9.77 g) and boron trifluoride etherate (2.0 ml). After stirring the mixture for one hour the cooling bath was removed and stirring was continued overnight. Then the reaction mixture was poured onto saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0→90:10) to give S)-2-benzyloxycarbonylamino-3-(1-phenyl-ethoxy)-propionic acid methyl ester (1.34 g, 47%) as a light yellow oil. MS (ISP): 358.2 ([M+H]+)). was removed stirring was continued overnight Then the reaction mixture was poured onto saturated sodium bicarbonate solution extracted with ethyl acetate The combined organic layers were washed with brine dried (MgSO4) concentrated The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0→90:10)

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

Procedure: To a stirred solution of (S)-1-benzyl 2-methyl aziridine-1,2-dicarboxylate (prepared according to the literature procedure: Org. Biomol. Chem., 2005, 3, 3357, 2.7 g, 11.4 mmol) in dichloromethane (30 mL), boron trifluoride etherate (0.01 mL, 0.11 mmol) was added at 0° C. followed by absolute ethanol (1.05 g, 22.9 mmol). The reaction mixture was stirred at room temperature for an hour, after which the solution was quenched with saturated bicarbonate solution (2 mL), extracted with dichloromethane (3×25 mL), organic layers were washed with water (25 mL), brine solution (25 mL) and dried over sodium sulfate. The removal of solvents afforded crude product, which was purified by silica gel column chromatography using a gradient of ethyl acetate in pet. ether. Yield: 2.0 g (63%). 1H NMR (400 MHz, DMSO-d6) δ: 1.08 (t, 3H), 3.38-3.46 (m, 2H), 3.57-3.63 (m, 2H), 3.70 (s, 3H), 4.26-4.31 (m, 1H), 5.04 (s, 2H), 7.30-7.39 (m, 5H), 7.73 (d, 1H). after which the solution was quenched with saturated bicarbonate solution (2 mL) extracted with dichloromethane (3×25 mL), organic layers were washed with water (25 mL), brine solution (25 mL) dried over sodium sulfate The removal of solvents afforded crude product, which was purified by silica gel column chromatography

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

Procedure: To a stirred solution of (S)-1-benzyl 2-methyl aziridine-1,2-dicarboxylate (prepared according to the literature procedure: Org. Biomol. Chem., 2005, 3, 3357, 2.7 g, 11.4 mmol) in dichloromethane (30 mL), boron trifluoride etherate (0.01 mL, 0.11 mmol) was added at 0° C. followed by absolute ethanol (1.05 g, 22.9 mmol). The reaction mixture was stirred at room temperature for an hour, after which the solution was quenched with saturated bicarbonate solution (2 mL), extracted with dichloromethane (3×25 mL), organic layers were washed with water (25 mL), brine solution (25 mL) and dried over sodium sulfate. The removal of solvents afforded crude product, which was purified by silica gel column chromatography using a gradient of ethyl acetate in pet. ether. Yield: 2.0 g (63%). 1H NMR (400 MHz, DMSO-d6) δ: 1.08 (t, 3H), 3.38-3.46 (m, 2H), 3.57-3.63 (m, 2H), 3.70 (s, 3H), 4.26-4.31 (m, 1H), 5.04 (s, 2H), 7.30-7.39 (m, 5H), 7.73 (d, 1H). after which the solution was quenched with saturated bicarbonate solution (2 mL) extracted with dichloromethane (3×25 mL), organic layers were washed with water (25 mL), brine solution (25 mL) dried over sodium sulfate The removal of solvents afforded crude product, which was purified by silica gel column chromatography

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

Procedure: To a 100 mL flask was added 1-benzyl 2-methyl aziridine-1,2-dicarboxylate (1 g, 4.25 mmol), dichloromethane (12 mL), (R)-1-Chloro-2-propanol (0.76 mL, 8.50 mmol), and boron trifluoride diethyl etherate (0.05 mL, 0.398 mmol). The mixture was stirred at room temperature for 15 minutes Solvent was removed in vacuo and the residue purified on silica gel eluting with Hexanes-EtOAc (0-50%) to give (R)-methyl 2-(benzyloxycarbonylamino)-3-(1-chloropropan-2-yloxy)propanoate (583 mg, 41%). MS [M+H] found 330.2. was removed in vacuo the residue purified on silica gel eluting with Hexanes-EtOAc (0-50%)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S,3S)-2,3-bis(benzyloxy)butane-1,4-diol (283 mg, 0.935 mmol), prepared as disclosed in Journal of Organic Chemistry 1991, 56(3), 1321-1322, and (S)-1-benzyl 2-methyl aziridine-1,2-dicarboxylate (110 mg, 0.468 mmol) in CH2Cl2 (1.5 mL) at −78° C. was added BF3-OEt2 (10 μL, 0.081 mmol), and the reaction mixture was stirred at −78° C. for 1 h, slowly warmed to 0° C., and then stirred at 0° C. for 3 h. The reaction mixture was directly purified by flash chromatography (SiO2) to afford the title compound as a colorless oil (208 mg, 83%): 1H NMR (400 MHz, CDCl3) δ 7.45-7.20 (m, 16H), 5.70 (d, J=8.5 Hz, 1H), 4.70-4.54 (m, 6H), 4.53-4.46 (m, 1H), 3.93 (dd, J=9.5, 3.2 Hz, 1H), 3.80-3.53 (m, 9H), 2.09-1.96 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 170.72, 156.04, 138.16, 138.08, 136.24, 128.54, 128.49, 128.47, 128.20, 128.13, 127.99, 127.91, 127.89, 127.86, 79.03, 78.10, 73.09, 72.88, 71.40, 71.08, 67.08, 61.40, 54.46, 52.60; ESIMS m/z 538.4 ([M+H]+). slowly warmed to 0° C. stirred at 0° C. for 3 h The reaction mixture was directly purified by flash chromatography (SiO2)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S,3S,4S)-2,3-bis(2-methylallyloxy)pentane-1,4-diol (920 milligrams (mg), 3.77 mmol) and (S)-1-benzyl 2-methyl aziridine-1,2-dicarboxylate (0.739 mL, 3.74 mmol) in anhydrous chloroform (CHCl3; 5 mL) was added BF3-Et2O (26 microliters (μL) 0.55 mmol) at 0° C. and the solution was stirred at 0° C. for 3 h. The crude reaction mixture was concentrated and purified by flash chromatography (SiO2) to furnish (S)-methyl 2-(benzyloxycarbonylamino)-3-((2S,3S,4S)-4-hydroxy-2,3-bis(2-methylallyloxy)-pentyloxy)-propanoate as a colorless oil (620 mg, 35%) and (S)-methyl 2-(benzyloxycarbonylamino)-3-((2S,3S,4S)-5-hydroxy-3,4-bis(2-methylallyloxy)pentan-2-yloxy)propanoate as a colorless oil (300 mg, 17%). The crude reaction mixture was concentrated purified by flash chromatography (SiO2)