(S)-环氧氯丙烷

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

实验步骤: (S)-epichlorohydrin (III, 98.9% enantiomerically pure, 99.3 chemical % purity, 4.9605 g, 53.61 mmol) is added to a slurry of potassium phthalimide (VI, 5.031 g, 27.161 mmol, 0.507 eq) and phthalimide (VI, 11.836 g, 80.45 mmol, 1.5006 eq) in DMF (32 ml) and the mixture stirred at 50° for 4.5 hrs. The mixture is added to methylene chloride (50 ml) and water (50 ml) added. The solids are removed by filtration with reduced pressure and washed with methylene chloride (20 ml). The phases are separated in the filtrate and the aqueous washed with methylene chloride (50 ml). The combined organics were washed with water (50 ml) and the aqueous backextraceted with methylene chloride (50 ml) after adding water (25 ml). The combined organics are dried over sodium sulfate and saturated with hydrogen chloride gas at 6°. Water (100 ml) is added and the phases separated. The aqueous phase is washed with methylene chloride (2×50 ml) and the combined organic phases are dried over sodium sulfate. The organic phase is concentrated under reduced pressure and toluene added (77 ml). The mixture is concentrated under reduced pressure to 31 g net weight and toluene (50 ml) and heptane (75 ml) added. The solids are filtered off and washed with toluene/heptane (1/1, 20 ml). The filtrate is concentrated under reduced pressure to 17 g net weight, heptane (100 ml) added and the mixture concentrated under reduced pressure to 15 g net weight. Heptane (100 ml) and methylene chloride (100 ml) is added and the mixture concentrated under reduced pressure to 130 g net weight. The solids are filtered off and washed with heptane/methylene chloride (2/1, 3×15 ml). The filtrate is concentrated under reduced pressure to 11 g net weight and toluene (90 ml) then heptane (400 ml) added. The resultant slurry is then cooled to −20° and the product collected by filtration with reduced pressure, washed with heptane and dried to give a crude solid. Flash chromatography of the crude solid (silica gel; eluting with a gradient of 15-45% ethyl acetate/cyclohexane) gives the title compound as an analytical sample, NMR 3.11, 3.62, 3.68, 3.87, 3.95, 4.14-4.20, 7.70-7.76 and 7.82-7.88δ; CMR 41.61, 47.27, 69.68, 123.53, 131.83, 134.26 and 168.65δ; MS (CI, NH3), M/Z (relative intensity) 259 (1.4), 257 (17), 242 (0.11), 240 (0.31), 221 (100); [α]25D=−33(C=0.712, CHCl3). NMR of the mosher ester derivative showed the product to have an enantiomeric purity of 96.2% upon comparison to the NMR of the mosher ester of the racemate. added The solids are removed by filtration with reduced pressure washed with methylene chloride (20 ml) The phases are separated in the filtrate the aqueous washed with methylene chloride (50 ml) The combined organics were washed with water (50 ml) after adding water (25 ml) The combined organics are dried over sodium sulfate and saturated with hydrogen chloride gas at 6° Water (100 ml) is added the phases separated The aqueous phase is washed with methylene chloride (2×50 ml) the combined organic phases are dried over sodium sulfate The organic phase is concentrated under reduced pressure and toluene added (77 ml) The mixture is concentrated under reduced pressure to 31 g net weight and toluene (50 ml) and heptane (75 ml) added The solids are filtered off washed with toluene/heptane (1/1, 20 ml) The filtrate is concentrated under reduced pressure to 17 g net weight, heptane (100 ml) added the mixture concentrated under reduced pressure to 15 g net weight Heptane (100 ml) and methylene chloride (100 ml) is added the mixture concentrated under reduced pressure to 130 g net weight The solids are filtered off washed with heptane/methylene chloride (2/1, 3×15 ml) The filtrate is concentrated under reduced pressure to 11 g net weight and toluene (90 ml) heptane (400 ml) added The resultant slurry is then cooled to −20° the product collected by filtration with reduced pressure washed with heptane dried to give a crude solid eluting with a gradient of 15-45% ethyl acetate/cyclohexane)

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

实验步骤: The sub-title compound was prepared according to the procedures described in steps (i) to (v) above for the synthesis of tert-butyl 2-[(4-cyanophenoxy)methyl]-1-aziridinecarboxylate, but using (S)-(+)-epichlorohydrin in place of epichlorohydrin in step (i).

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

实验步骤: Alternatively, reaction of 2-nitroimidazole, anhydrous potassium carbonate, and (S)-(+)-epichlorohydrin as described in Example 1(a) gives the product. gives the product

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

实验步骤: S-epichlorohydrin (III, 98.9% enantiomerically pure, 99.3 chemical % purity, 4.9605 g, 53.61 mmol) is added to a slurry of potassium phthalimide (VI, 5.031 g, 27.161 mmol, 0.507 eq) and phthalimide (VI, 11.836 g, 80.45 mmol, 1.5006 eq) in DMF (32 ml) and the mixture stirred at 50° for 4.5 hrs. The mixture is added to methylene chloride (50 ml) and water (50 ml) added. The solids are removed by filtration with reduced pressure and washed with methylene chloride (20 ml). The phases are separated in the filtrate and the aqueous washed with methylene chloride (50 ml). The combined organics were washed with water (50 ml) and the aqueous backextraceted with methylene chloride (50 ml) after adding water (25 ml). The combined organics are dried over sodium sulfate and saturated with hydrogen chloride gas at 6°. Water (100 ml) is added and the phases separated. The aqueous phase is washed with methylene chloride (2×50 ml) and the combined organic phases are dried over sodium sulfate. The organic phase is concentrated under reduced pressure and toluene added (77 ml). The mixture is concentrated under reduced pressure to 31 g net weight and toluene (50 ml) and heptane (75 ml) added. The solids are filtered off and washed with toluene/heptane (1/1, 20 ml). The filtrate is concentrated under reduced pressure to 17 g net weight, heptane (100 ml) added and the mixture concentrated under reduced pressure to 15 g net weight. Heptane (100 ml) and methylene chloride (100 ml) is added and the mixture concentrated under reduced pressure to 130 g net weight. The solids are filtered off and washed with heptane/methylene chloride (2/1, 3×15 ml). The filtrate is concentrated under reduced pressure to 11 g net weight and toluene (90 ml) then heptane (400 ml) added. The resultant slurry is then cooled to −20° and the product collected by filtration under reduced pressure, washed with heptane and dried to give a crude solid. Flash chromatography of the crude solid (silica gel; eluting with a gradient of 15-45% ethyl acetate/cyclohexane) gives the title compound as an analytical sample, NMR 3.11, 3.62, 3.68, 3.87, 3.95, 4.14-4.20, 7.70-7.76 and 7.82-7.88 δ; CMR 41.61, 47.27, 69.68, 123.53, 131.83, 134.26 and 168.65 δ; MS (CI, NH3), M/Z (relative intensity) 259 (1.4), 257 (17), 242 (0.11), 240 (0.31), 221 (100); [α]25D=−33 (C=0.712, CHCl3). NMR of the mosher ester derivative showed the product to have an enantiomeric purity of 96.2% upon comparison to the NMR of the mosher ester of the racemate. added The solids are removed by filtration with reduced pressure washed with methylene chloride (20 ml) The phases are separated in the filtrate the aqueous washed with methylene chloride (50 ml) The combined organics were washed with water (50 ml) after adding water (25 ml) The combined organics are dried over sodium sulfate and saturated with hydrogen chloride gas at 6° Water (100 ml) is added the phases separated The aqueous phase is washed with methylene chloride (2×50 ml) the combined organic phases are dried over sodium sulfate The organic phase is concentrated under reduced pressure and toluene added (77 ml) The mixture is concentrated under reduced pressure to 31 g net weight and toluene (50 ml) and heptane (75 ml) added The solids are filtered off washed with toluene/heptane (1/1, 20 ml) The filtrate is concentrated under reduced pressure to 17 g net weight, heptane (100 ml) added the mixture concentrated under reduced pressure to 15 g net weight Heptane (100 ml) and methylene chloride (100 ml) is added the mixture concentrated under reduced pressure to 130 g net weight The solids are filtered off washed with heptane/methylene chloride (2/1, 3×15 ml) The filtrate is concentrated under reduced pressure to 11 g net weight and toluene (90 ml) heptane (400 ml) added The resultant slurry is then cooled to −20° the product collected by filtration under reduced pressure washed with heptane dried to give a crude solid eluting with a gradient of 15-45% ethyl acetate/cyclohexane)

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

实验步骤: S-epichlorohydrin (III, 98.9% enantiomerically pure, 99.3 chemical % purity, 4.9605 g, 53.61 mmol) is added to a slurry of potassium phthalimide (VI, 5.031 g, 27.161 mmol, 0.507 eq) and phthalimide (VI, 11.836 g, 80.45 mmol, 1.5006 eq) in DMF (32 ml) and the mixture stirred at 50° for 4.5 hrs. The mixture is added to methylene chloride (50 ml) and water (50 ml) added. The solids are removed by filtration with reduced pressure and washed with methylene chloride (20 ml). The phases are separated in the filtrate and the aqueous washed with methylene chloride (50 ml). The combined organics were washed with water (50 ml) and the aqueous backextraceted with methylene chloride (50 ml) after adding water (25 ml). The combined organics are dried over sodium sulfate and saturated with hydrogen chloride gas at 6°. Water (100 ml) is added and the phases separated. The aqueous phase is washed with methylene chloride (2×50 ml) and the combined organic phases are dried over sodium sulfate. The organic phase is concentrated under reduced pressure and toluene added (77 ml). The mixture is concentrated under reduced pressure to 31 g net weight and toluene (50 ml) and heptane (75 ml) added. The solids are filtered off and washed with toluene/heptane (1/1, 20 ml). The filtrate is concentrated under reduced pressure to 17 g net weight, heptane (100 ml) added and the mixture concentrated under reduced pressure to 15 g net weight. Heptane (100 ml) and methylene chloride (100 ml) is added and the mixture concentrated under reduced pressure to 130 g net weight. The solids are filtered off and washed with heptane/methylene chloride (2/1, 3×15 ml). The filtrate is concentrated under reduced pressure to 11 g net weight and toluene (90 ml) then heptane (400 ml) added. The resultant slurry is then cooled to −20° and the product collected by filtration under reduced pressure, washed with heptane and dried to give a crude solid. Flash chromatography of the crude solid (silica gel; eluting with a gradient of 15-45% ethyl acetate/cyclohexane) gives the title compound as an analytical sample, NMR 3.11, 3.62, 3.68, 3.87, 3.95, 4.14-4.20, 7.70-7.76 and 7.82-7.88 δ; CMR 41.61, 47.27, 69.68, 123.53, 131.83, 134.26 and 168.65 δ; MS (CI, NH3), M/Z (relative intensity) 259 (1.4), 257 (17), 242 (0.11), 240 (0.31), 221 (100); [α]25D=−33 (C=0.712, CHCl3). NMR of the mosher ester derivative showed the product to have an enantiomeric purity of 96.2% upon comparison to the NMR of the mosher ester of the racemate. added The solids are removed by filtration with reduced pressure washed with methylene chloride (20 ml) The phases are separated in the filtrate the aqueous washed with methylene chloride (50 ml) The combined organics were washed with water (50 ml) after adding water (25 ml) The combined organics are dried over sodium sulfate and saturated with hydrogen chloride gas at 6° Water (100 ml) is added the phases separated The aqueous phase is washed with methylene chloride (2×50 ml) the combined organic phases are dried over sodium sulfate The organic phase is concentrated under reduced pressure and toluene added (77 ml) The mixture is concentrated under reduced pressure to 31 g net weight and toluene (50 ml) and heptane (75 ml) added The solids are filtered off washed with toluene/heptane (1/1, 20 ml) The filtrate is concentrated under reduced pressure to 17 g net weight, heptane (100 ml) added the mixture concentrated under reduced pressure to 15 g net weight Heptane (100 ml) and methylene chloride (100 ml) is added the mixture concentrated under reduced pressure to 130 g net weight The solids are filtered off washed with heptane/methylene chloride (2/1, 3×15 ml) The filtrate is concentrated under reduced pressure to 11 g net weight and toluene (90 ml) heptane (400 ml) added The resultant slurry is then cooled to −20° the product collected by filtration under reduced pressure washed with heptane dried to give a crude solid eluting with a gradient of 15-45% ethyl acetate/cyclohexane)

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

实验步骤: Alternatively, a mixture of 2-nitroimidazole, anhydrous potassium carbonate, and (S)-(+)-epichlorohydrin is refluxed for 10 minutes then filtered while hot. The filtrate is concentrated and cooled to give a solid. Crystallization from ethanol and further processing gives the product. is refluxed for 10 minutes then filtered while hot The filtrate is concentrated cooled to give a solid Crystallization from ethanol and further processing gives the product

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

实验步骤: Alternatively, a mixture of 2-nitroimidazole, anhydrous potassium carbonate, and (S)-(+)-epichlorohydrin is refluxed for 10 minutes then filtered while hot. The filtrate is concentrated and cooled to give a solid. Crystallization from ethanol and further processing gives the product. is refluxed for 10 minutes then filtered while hot The filtrate is concentrated cooled to give a solid Crystallization from ethanol and further processing gives the product

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibenzylamine (39.4 g, 0.20 mol) and ferric chloride (12.6 g. 0.30 mol) were added to 100 mL of acetonitrile. The mixture was stirred at 25° C. for 30 minutes. (S)-epichlorohydrin (18.6 g, 0.2 mol) was then added and stirred at 60° C. for 8 hours. Filtered and the solvent was evaporated to provide 55 g of colorless oil in 94% yield. HPLC: 98%. stirred at 60° C. for 8 hours Filtered the solvent was evaporated

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibenzylamine (39.4 g, 0.20 mol) and ferric chloride (12.6 g. 0.30 mol) were added to 100 mL of acetonitrile. The mixture was stirred at 25° C. for 30 minutes. (S)-epichlorohydrin (18.6 g, 0.2 mol) was then added and stirred at 60° C. for 8 hours. Filtered and the solvent was evaporated to provide 55 g of colorless oil in 94% yield. HPLC: 98%. stirred at 60° C. for 8 hours Filtered the solvent was evaporated

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibenzylamine (39.4 g, 0.20 mol) and ferric chloride (12.6 g. 0.30 mol) were added to 100 mL of ether. The mixture was stirred at 25° C. for 30 minutes, (S)-epichlorohydrin (18.6 g, 0.2 mol) was then added and stirred for at 60° C. 8 hours. Filtered and the solvent was evaporated to provide 53 g of colorless oil in 92% yield. HPLC: 99%. stirred for at 60° C 8 hours Filtered the solvent was evaporated

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibenzylamine (39.4 g, 0.20 mol) and lithium chloride (12.6 g, 0.30 mol) were added to 100 mL of toluene. The mixture was stirred at 25° C. for 30 minutes. (S)-epichlorohydrin (18.6 g, 0.2 mol) was then added and stirred at 60° C. for 8 hours. The mixture was filtered and the solvent was evaporated to provide 52 g of colorless oil in 90% yield. HPLC: 99.3%. stirred at 60° C. for 8 hours The mixture was filtered the solvent was evaporated

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibenzylamine (39.4 g, 0.20 mol) and lithium chloride (12.6 g, 0.30 mol) were added to 100 mL of toluene. The mixture was stirred at 25° C. for 30 minutes. (S)-epichlorohydrin (18.6 g, 0.2 mol) was then added and stirred at 60° C. for 8 hours. The mixture was filtered and the solvent was evaporated to provide 52 g of colorless oil in 90% yield. HPLC: 99.3%. stirred at 60° C. for 8 hours The mixture was filtered the solvent was evaporated