tert-butyl 3,6-dihydro-2H-pyridine-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of m-CPBA (7.53 g, 32.7 mmol) in DCM (10 mL) was added to a solution of tert-butyl 5,6-dihydropyridine-1(2H)-carboxylate (5.00 g, 27.3 mmol) in DCM (20 mL) at 0° C. The reaction was stirred at 0° C. for 15 minutes and then at room temperature for 3 hours. Saturated sodium sulfite solution (20 mL) and saturated sodium bicarbonate solution (30 mL) was added. The organic layer was separated, washed with brine, dried (sodium sulfate) and concentrated in vacuo to give tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (5.36 g, 99%) as oil. at room temperature for 3 hours The organic layer was separated washed with brine dried (sodium sulfate) concentrated in vacuo

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

実験手順: To a stirred solution of 3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (19.1 mmol, 3.5 g), in DCM (50 mL) cooled at 0° C., was added m-CPBA (32.2 mmol, 5.95 g (70%)) portion wise. The reaction was stirred at room temperature for 4 h. The reaction was diluted with DCM (50 mL) and washed with sat. Na2S2O3, sat. NaHCO3, water and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a SiO2 cartridge (5% EtOAc in hexane -25% EtOAc in hexane) to provide 7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester. washed with sat. Na2S2O3, sat. NaHCO3, water and brine dried (Na2SO4) filtered concentrated under reduced pressure The residue was purified on a SiO2 cartridge (5% EtOAc in hexane -25% EtOAc in hexane)

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

実験手順: To a solution of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine (18.9 g) in dichloromethane (400 ml). was added in turn sodium hydrogen carbonate (11.3 g) and m-chloroperoxybenzoic acid (23.4 g) with care at 0° C., and which was stirred for 2 hours. Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was dissolved in n-hexane (300 ml) and insoluble material was removed by filtration. Mother liquor was concentrated in vacuo, the remainings were dissolved in ethyl acetate (300 ml) and washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2), which was dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane. Tractions, containing desired product, were collected and concentrated in vacuo to give 1-tert-butoxycarbonyl-3,4-epoxypiperidine (13.7 g). Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) dried over magnesium sulfate Evaporation of the solvent gave a residue, which insoluble material was removed by filtration Mother liquor was concentrated in vacuo the remainings were dissolved in ethyl acetate (300 ml) washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2) which was dried over magnesium sulfate Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane Tractions, containing desired product were collected concentrated in vacuo

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

実験手順: To a solution of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine (18.9 g) in dichloromethane (400 ml). was added in turn sodium hydrogen carbonate (11.3 g) and m-chloroperoxybenzoic acid (23.4 g) with care at 0° C., and which was stirred for 2 hours. Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was dissolved in n-hexane (300 ml) and insoluble material was removed by filtration. Mother liquor was concentrated in vacuo, the remainings were dissolved in ethyl acetate (300 ml) and washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2), which was dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane. Tractions, containing desired product, were collected and concentrated in vacuo to give 1-tert-butoxycarbonyl-3,4-epoxypiperidine (13.7 g). Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) dried over magnesium sulfate Evaporation of the solvent gave a residue, which insoluble material was removed by filtration Mother liquor was concentrated in vacuo the remainings were dissolved in ethyl acetate (300 ml) washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2) which was dried over magnesium sulfate Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane Tractions, containing desired product were collected concentrated in vacuo

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

実験手順: To a stirred solution of 3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (Aldrich, 15.99 g, 87.28 mmol) in methylene chloride (600 mL) at 0° C., mCPBA (Aldrich, 29.4 g, 77%, 131 mmol) was added and the mixture was stirred overnight. The reaction was quenched with 10% Na2S2O3 and the organic layer was separated and washed with 5% sodium carbonate, brine and water and dried over sodium sulfate and concentrated to give a light yellow oil, which was chromatographied (10% EtOAc/Hexane) to yield a colorless oil. 14.93 g. The compound was used directly for the next step. The reaction was quenched with 10% Na2S2O3 the organic layer was separated washed with 5% sodium carbonate, brine and water dried over sodium sulfate concentrated to give a light yellow oil, which to yield a colorless oil

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of m-CPBA (7.53 g, 32.7 mmol) in DCM (10 mL) was added to a solution of tert-butyl 5,6-dihydropyridine-1(2H)-carboxylate (5.00 g, 27.3 mmol) in DCM (20 mL) at 0° C. The reaction was stirred at 0° C. for 15 minutes and then at room temperature for 3 hours. Saturated sodium sulfite solution (20 mL) and saturated sodium bicarbonate solution (30 mL) was added. The organic layer was separated, washed with brine, dried (sodium sulfate) and concentrated in vacuo to give tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (5.36 g, 99%) as oil. at room temperature for 3 hours The organic layer was separated washed with brine dried (sodium sulfate) concentrated in vacuo

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

実験手順: To a solution of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine (18.9 g) in dichloromethane (400 ml) was added in turn sodium hydrogen carbonate (11.3 g) and m-chloroperoxybenzoic acid (23.4 g) with care at 0° C., and which was stirred for 2 hours. Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was dissolved in n-hexane (300 ml) and insoluble material was removed by filtration. Mother liquor was concentrated in vacuo, the remainings were dissolved in ethyl acetate (300 ml) and washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2), which was dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane. Fractions, containing desired product, were collected and concentrated in vacuo to give 1-tert-butoxycarbonyl-3,4-epoxypiperidine (13.7 g). Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) dried over magnesium sulfate Evaporation of the solvent gave a residue, which insoluble material was removed by filtration Mother liquor was concentrated in vacuo the remainings were dissolved in ethyl acetate (300 ml) washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2) which was dried over magnesium sulfate Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane Fractions, containing desired product were collected concentrated in vacuo

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

実験手順: To a solution of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine (18.9 g) in dichloromethane (400 ml) was added in turn sodium hydrogen carbonate (11.3 g) and m-chloroperoxybenzoic acid (23.4 g) with care at 0° C., and which was stirred for 2 hours. Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was dissolved in n-hexane (300 ml) and insoluble material was removed by filtration. Mother liquor was concentrated in vacuo, the remainings were dissolved in ethyl acetate (300 ml) and washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2), which was dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane. Fractions, containing desired product, were collected and concentrated in vacuo to give 1-tert-butoxycarbonyl-3,4-epoxypiperidine (13.7 g). Insoluble material was removed by filtration, mother liquor was washed saturated sodium chloride in water (100 ml) dried over magnesium sulfate Evaporation of the solvent gave a residue, which insoluble material was removed by filtration Mother liquor was concentrated in vacuo the remainings were dissolved in ethyl acetate (300 ml) washed in turn with saturated sodium hydrogen carbonate in water (100 ml×5) and saturated sodium chloride in water (100 ml×2) which was dried over magnesium sulfate Evaporation of the solvent gave a residue, which was chromatographed on silica gel (350 ml) eluting in turn with 10%, 20% and 30% ethyl acetate in n-hexane Fractions, containing desired product were collected concentrated in vacuo