tert-butyl N-(3-oxocyclobutyl)carbamate

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

実験手順: To a 0° C. cold solution of 2.00 g (10.8 mmol) of (3-oxo-cyclobutyl)-carbamic acid tert-butyl ester in 20 mL of ethanol was added portionwise 204 mg (5.40 mmol) of sodium borohydride. The reaction mixture was stirred at room temperature until complete conversion was achieved. The solvent was evaporated, the crude product was taken up in dichloromethane and treated with sat. sodium bicarbonate solution. The phases were separated and the aqueous phase extracted twice with dichloromethane. The organic phases were combined, dried over magnesium sulfate and concentrated to give crude (3-hydroxy-cyclobutyl)-carbamic acid tert-butyl ester. Rt=0.76 min (Method C). Detected mass: 132.2 (M-tBu+H+). The solvent was evaporated treated with sat. sodium bicarbonate solution The phases were separated the aqueous phase extracted twice with dichloromethane dried over magnesium sulfate concentrated

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

実験手順: To a vigorously stirring solution of N-Boc-3-methylene-cyclobutanamine (9.8 g, 53.5 mmol) in DCM (160 mL) and H2O (160 mL) was added K2CO3 (3 g, 21.7 mmol), followed by NaClO4 (35 g, 163.5 mmol), tetrabutylammonium chloride (0.2 g, 0.72 mmol) and RuCl3 (0.6 g, 7.6 mmol). During the course of the reaction, the organic solution turned dark brown, the catalyst turned black, while the upper aqueous layer turned white. The reaction was monitored by TLC, and upon completion, the reaction mixture was filtered through a pad of celite. The filtrates were transferred to a separatory funnel, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%) to yield the desired N-Boc-3-amino-cyclobutanone (7.13 g, 38.53 mmol, 72% yield): NMR (250 MHz, CDCl3) δ 4.88 (bs, 1 H), 4.13-4.29 (m, 1 H), 3.23-3.41 (m, 2 H), 2.9-3.05 (m, 2 H), 1.39 (s, 9 H). During the course of the reaction upon completion, the reaction mixture was filtered through a pad of celite The filtrates were transferred to a separatory funnel the aqueous layer was extracted with DCM (2×50 mL) The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL) dried over Na2SO4 filtered evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%)

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

実験手順: To a vigorously stirring solution of N-Boc-3-methylene-cyclobutanamine (9.8 g, 53.5 mmol) in DCM (160 mL) and H2O (160 mL) was added K2CO3 (3 g, 21.7 mmol), followed by NaIO4 (35 g, 163.5 mmol), tetrabutylammonium chloride (0.2 g, 0.72 mmol) and RuCl3 (0.6 g, 7.6 mmol). During the course of the reaction, the organic solution turned dark brown, the catalyst turned black, while the upper aqueous layer turned white. The reaction was monitored by TLC, and upon completion, the reaction mixture was filtered through a pad of celite. The filtrates were transferred to a separatory funnel, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%) to yield the desired N-Boc-3-amino-cyclobutanone (7.13 g, 38.53 mmol, 72% yield): NMR (250 MHz, CDCl3) δ 4.88 (bs, 1 H), 4.13-4.29 (m, 1 H), 3.23-3.41 (m, 2 H), 2.9-3.05 (m, 2 H), 1.39 (s, 9 H). During the course of the reaction upon completion, the reaction mixture was filtered through a pad of celite The filtrates were transferred to a separatory funnel the aqueous layer was extracted with DCM (2×50 mL) The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL) dried over Na2SO4 filtered evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%)

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

実験手順: To a vigorously stirring solution of N-Boc-3-methylene-cyclobutanamine (9.8 g, 53.5 mmol) in DCM (160 mL) and H2O (160 mL) was added K2CO3 (3 g, 21.7 mmol), followed by NaIO4 (35 g, 163.5 mmol), tetrabutylammonium chloride (0.2 g, 0.72 mmol) and RuCl3 (0.6 g, 7.6 mmol). During the course of the reaction, the organic solution turned dark brown, the catalyst turned black, while the upper aqueous layer turned white. The reaction was monitored by TLC, and upon completion, the reaction mixture was filtered through a pad of celite. The filtrates were transferred to a separatory funnel, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%) to yield the desired N-Boc-3-amino-cyclobutanone (7.13 g, 38.53 mmol, 72% yield): NMR (250 MHz, CDCl3) δ 4.88 (bs, 1H), 4.13-4.29 (m, 1H), 3.23-3.41 (m, 2H), 2.9-3.05 (m, 2H), 1.39 (s, 9H). During the course of the reaction upon completion, the reaction mixture was filtered through a pad of celite The filtrates were transferred to a separatory funnel the aqueous layer was extracted with DCM (2×50 mL) The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL) dried over Na2SO4 filtered evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%)

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 3-oxocyclobutylcarbamate (2.2 g, 11.9 mmol), 2-methylpropane-2-sulfinamide (1.6 g, 13.1 mmol), Ti(OEt)4 (5.5 g, 24 mmol) in 20 mL of THF was stirred at 50-60° C. overnight. The mixture was cooled to room temperature and then quenched with saturated NH4Cl solution. The formed solid was removed by filtration. The filtrate was evaporated to dryness and the crude residue was purified by silica gel chromatography (200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (4:1)) to give tert-butyl 3-(tert-butylsulfinylimino)cyclobutylcarbamate as clear oil (2.0 g, 58%). MS: (M+H)+=289.1; 1H NMR (300 MHz, CDCl3): δ 5.08 (m, 1H), 4.29 (s, 1H), 3.42-3.00 (m, 4H), 1.43 (s, 9H), 1.22 (s, 9H). The mixture was cooled to room temperature quenched with saturated NH4Cl solution The formed solid was removed by filtration The filtrate was evaporated to dryness the crude residue was purified by silica gel chromatography (200-300 mesh eluting with a mixture of petroleum ether and ethyl acetate (4:1))

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 3-oxocyclobutylcarbamate (2.2 g, 11.9 mmol), 2-methylpropane-2-sulfinamide (1.6 g, 13.1 mmol), Ti(OEt)4 (5.5 g, 24 mmol) in 20 mL of THF was stirred at 50-60° C. overnight. The mixture was cooled to room temperature and then quenched with saturated NH4Cl solution. The formed solid was removed by filtration. The filtrate was evaporated to dryness and the crude residue was purified by silica gel chromatography (200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (4:1)) to give tert-butyl 3-(tert-butylsulfinylimino)cyclobutylcarbamate as clear oil (2.0 g, 58%). MS: (M+H)+=289.1; 1H NMR (300 MHz, CDCl3): δ 5.08 (m, 1H), 4.29 (s, 1H), 3.42-3.00 (m, 4H), 1.43 (s, 9H), 1.22 (s, 9H). The mixture was cooled to room temperature quenched with saturated NH4Cl solution The formed solid was removed by filtration The filtrate was evaporated to dryness the crude residue was purified by silica gel chromatography (200-300 mesh eluting with a mixture of petroleum ether and ethyl acetate (4:1))

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

実験手順: To a vigorously stirring solution of N-Boc-3-methylene-cyclobutanamine (9.8 g, 53.5 mmol) in DCM (160 mL) and H2O (160 mL) was added K2CO3 (3 g, 21.7 mmol), followed by NaIO4 (35 g, 163.5 mmol), tetrabutylammonium chloride (0.2 g, 0.72 mmol) and RuCl3 (0.6 g, 7.6 mmol). During the course of the reaction, the organic solution turned dark brown, the catalyst turned black, while the upper aqueous layer turned white. The reaction was monitored by TLC, and upon completion, the reaction mixture was filtered through a pad of celite. The filtrates were transferred to a separatory funnel, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%) to yield the desired N-Boc-3-amino-cyclobutanone (7.13 g, 38.53 mmol, 72% yield): NMR (250 MHz, CDCl3) δ 4.88 (bs, 1 H), 4.13-4.29 (m, 1 H), 3.23-3.41 (m, 2 H), 2.9-3.05 (m, 2 H), 1.39 (s, 9 H). During the course of the reaction upon completion, the reaction mixture was filtered through a pad of celite The filtrates were transferred to a separatory funnel the aqueous layer was extracted with DCM (2×50 mL) The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL) dried over Na2SO4 filtered evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%)

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

実験手順: To a vigorously stirring solution of N-Boc-3-methylene-cyclobutanamine (9.8 g, 53.5 mmol) in DCM (160 mL) and H2O (160 mL) was added K2CO3 (3 g, 21.7 mmol), followed by NaIO4 (35 g, 163.5 mmol), tetrabutylammonium chloride (0.2 g, 0.72 mmol) and RuCl3 (0.6 g, 7.6 mmol). During the course of the reaction, the organic solution turned dark brown, the catalyst turned black, while the upper aqueous layer turned white. The reaction was monitored by TLC, and upon completion, the reaction mixture was filtered through a pad of celite. The filtrates were transferred to a separatory funnel, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%) to yield the desired N-Boc-3-amino-cyclobutanone (7.13 g, 38.53 mmol, 72% yield): NMR (250 MHz, CDCl3) δ 4.88 (bs, 1H), 4.13-4.29 (m, 1H), 3.23-3.41 (m, 2H), 2.9-3.05 (m, 2H), 1.39 (s, 9H). During the course of the reaction upon completion, the reaction mixture was filtered through a pad of celite The filtrates were transferred to a separatory funnel the aqueous layer was extracted with DCM (2×50 mL) The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL) dried over Na2SO4 filtered evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%)

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

実験手順: To a solution of (3-oxo-cyclobutyl)-carbamic acid tert-butyl ester (5.6 g, 30 2 mmol) in anhydrous toluene (100 mL) was added methyl (triphenylphosphoranylidene)acetate (10.7 g, 45.4 mmol) and heated to reflux overnight under N2. After cooling to room temperature, the mixture was poured into water and extracted with EA. The organic phase was dried over Na2SO4, concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1) to give the title compound (7 g, yield 96%) as a white solid. heated to reflux overnight under N2 extracted with EA The organic phase was dried over Na2SO4 concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1)

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

実験手順: To a solution of (3-oxo-cyclobutyl)-carbamic acid tert-butyl ester (5.6 g, 30 2 mmol) in anhydrous toluene (100 mL) was added methyl (triphenylphosphoranylidene)acetate (10.7 g, 45.4 mmol) and heated to reflux overnight under N2. After cooling to room temperature, the mixture was poured into water and extracted with EA. The organic phase was dried over Na2SO4, concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1) to give the title compound (7 g, yield 96%) as a white solid. heated to reflux overnight under N2 extracted with EA The organic phase was dried over Na2SO4 concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1)

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

実験手順: To a solution of (3-oxo-cyclobutyl)-carbamic acid tert-butyl ester (5.6 g, 30.2 mmol) in anhydrous toluene (100 mL) was added methyl (triphenylphosphoranylidene)acetate (10.7 g, 45.4 mmol) and heated to reflux overnight under N2. After cooling to room temperature, the mixture was poured into water and extracted with EA. The organic phase was dried over Na2SO4, concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1) to give the title compound (7 g, yield 96%) as a white solid. heated to reflux overnight under N2 extracted with EA The organic phase was dried over Na2SO4 concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1)

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

実験手順: To a solution of (3-oxo-cyclobutyl)-carbamic acid tert-butyl ester (5.6 g, 30.2 mmol) in anhydrous toluene (100 mL) was added methyl (triphenylphosphoranylidene)acetate (10.7 g, 45.4 mmol) and heated to reflux overnight under N2. After cooling to room temperature, the mixture was poured into water and extracted with EA. The organic phase was dried over Na2SO4, concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1) to give the title compound (7 g, yield 96%) as a white solid. heated to reflux overnight under N2 extracted with EA The organic phase was dried over Na2SO4 concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=20:1)