tert-butyl 1-(2-oxoethyl)cyclopropane-1-carboxylate

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

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

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: 4.0 g (21.9 mmol) of tert-butyl 1-(prop-2-en-1-yl)cyclopropanecarboxylate were dissolved in 70 ml of methanol and 30 ml of dichloromethane. At −78° C., ozone in a stream of O2 was passed through the reaction solution for 45 min using an ozone generator. Once the color of the solution had changed to light blue, the reaction solution was flushed with pure oxygen until the color had disappeared again. 6.5 ml (88.9 mmol) of dimethyl sulfide were then added, and the reaction solution was slowly warmed to RT. The mixture was concentrated on a rotary evaporator and the residue was purified by chromatography on silica gel (mobile phase gradient cyclohexane/ethyl acetate 50:1, 30:1, 20:1, 10:1). This gave 1.87 g (44.1% of theory) of the target compound. was flushed with pure oxygen until the color The mixture was concentrated on a rotary evaporator the residue was purified by chromatography on silica gel (mobile phase gradient cyclohexane/ethyl acetate 50:1, 30:1, 20:1, 10:1)

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

Procedure: 10.5 g (54.7 mmol, 1 eq.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 eq.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 eq.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at RT (IPC by GC). A solution of 2 ml (0.64 eq.) AcOH in 15 ml toluene was added. After 30 min at RT, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. NaHCO3 solution was added over 40 min (foaming). 50 ml EtOAc were added. The mixture was stirred for 30 min at RT. The mixture was extracted with 200 ml and a second time with 50 ml EtOAc. The organic phases were washed with 50 ml sat. aq. NaHCO3 solution followed by 50 ml sat. aq. NaCl solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material). After 30 min at RT the reaction mixture was cooled to 0° C. The mixture was stirred for 30 min at RT The mixture was extracted with 200 ml The organic phases were washed with 50 ml sat. aq. NaHCO3 solution dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g (36.34 mmol, 1 eq., 96% a % by GC) 1-allyl-cyclopropanecarboxylic acid tert-butyl ester were dissolved in 40 ml CH2Cl2 and 40 ml MeOH. The solution was cooled to −72° C. and the ozone was bubbled through the reaction mixture until a blue color was obtained. Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained. 10 ml (3.68 eq.) dimethyl sulfide and 14 ml (2.76 eq.) triethylamine were added. The reaction mixture was warmed to RT and stirred overnight at that temperature (peroxide test negative, pH 7-8). The yellowish reaction mixture was added to 100 ml sat. aq. ammonium chloride solution (exothermic) and extracted 3 times with 70 ml CH2Cl2. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (CH2Cl2; TLC:EtOAc/heptane 1:2) to provide 3.90 g (96% GC, 56% yield) of the title compound as an oil. the ozone was bubbled through the reaction mixture until a blue color was obtained Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained The reaction mixture was warmed to RT The yellowish reaction mixture extracted 3 times with 70 ml CH2Cl2 dried over sodium sulfate filtered concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (CH2Cl2; TLC:EtOAc/heptane 1:2)

Conditions: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g (36.34 mmol, 1 eq., 96% a % by GC) 1-allyl-cyclopropanecarboxylic acid tert-butyl ester were dissolved in 40 ml CH2Cl2 and 40 ml MeOH. The solution was cooled to −72° C. and the ozone was bubbled through the reaction mixture until a blue color was obtained. Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained. 10 ml (3.68 eq.) dimethyl sulfide and 14 ml (2.76 eq.) triethylamine were added. The reaction mixture was warmed to RT and stirred overnight at that temperature (peroxide test negative, pH 7-8). The yellowish reaction mixture was added to 100 ml sat. aq. ammonium chloride solution (exothermic) and extracted 3 times with 70 ml CH2Cl2. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (CH2Cl2; TLC:EtOAc/heptane 1:2) to provide 3.90 g (96% GC, 56% yield) of the title compound as an oil. the ozone was bubbled through the reaction mixture until a blue color was obtained Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained The reaction mixture was warmed to RT The yellowish reaction mixture extracted 3 times with 70 ml CH2Cl2 dried over sodium sulfate filtered concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (CH2Cl2; TLC:EtOAc/heptane 1:2)

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

Procedure: 10.5 g (54.7 mmol, 1 eq.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 eq.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 eq.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at room temperature (IPC by GC). A solution of 2 ml (0.64 eq.) acetic acid in 15 ml toluene was added. After 30 min at room temperature, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. sodium hydrogencarbonate solution was added over 40 min (foaming). 50 ml ethyl acetate were added. The mixture was stirred for 30 min at room temperature. The mixture was extracted with 200 ml and a second time with 50 ml ethyl acetate. The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution followed by 50 ml sat. aq. sodium chloride solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material). After 30 min at room temperature the reaction mixture was cooled to 0° C. The mixture was stirred for 30 min at room temperature The mixture was extracted with 200 ml The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g (36.34 mmol, 1 eq., 96% a % by GC) 1-allyl-cyclopropanecarboxylic acid tert-butyl ester were dissolved in 40 ml dichloromethane and 40 ml methanol. The solution was cooled to −72° C. and the ozone was bubbled through the reaction mixture until a blue color was obtained. Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained. 10 ml (3.68 eq.) dimethyl sulfide and 14 ml (2.76 eq.) triethylamine were added. The reaction mixture was warmed to room temperature and stirred overnight at that temperature (peroxide test negative, pH 7-8). The yellowish reaction mixture was added to 100 ml sat. aq. ammonium chloride solution (exothermic) and extracted 3 times with 70 ml dichloromethane. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (dichloromethane; TLC: ethyl acetate/heptane 1:2) to provide 3.90 g (96% GC, 56% yield) of the title compound as an oil. the ozone was bubbled through the reaction mixture until a blue color was obtained Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained The reaction mixture was warmed to room temperature The yellowish reaction mixture extracted 3 times with 70 ml dichloromethane dried over sodium sulfate filtered concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (dichloromethane; TLC: ethyl acetate/heptane 1:2)

Conditions: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g (36.34 mmol, 1 eq., 96% a % by GC) 1-allyl-cyclopropanecarboxylic acid tert-butyl ester were dissolved in 40 ml dichloromethane and 40 ml methanol. The solution was cooled to −72° C. and the ozone was bubbled through the reaction mixture until a blue color was obtained. Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained. 10 ml (3.68 eq.) dimethyl sulfide and 14 ml (2.76 eq.) triethylamine were added. The reaction mixture was warmed to room temperature and stirred overnight at that temperature (peroxide test negative, pH 7-8). The yellowish reaction mixture was added to 100 ml sat. aq. ammonium chloride solution (exothermic) and extracted 3 times with 70 ml dichloromethane. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (dichloromethane; TLC: ethyl acetate/heptane 1:2) to provide 3.90 g (96% GC, 56% yield) of the title compound as an oil. the ozone was bubbled through the reaction mixture until a blue color was obtained Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained The reaction mixture was warmed to room temperature The yellowish reaction mixture extracted 3 times with 70 ml dichloromethane dried over sodium sulfate filtered concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (dichloromethane; TLC: ethyl acetate/heptane 1:2)

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

Procedure: 10.5 g (54.7 mmol, 1 equiv.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 equiv.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 equiv.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at room temperature (IPC by GC). A solution of 2 ml (0.64 equiv.) acetic acid in 15 ml toluene was added. After 30 min at room temperature, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. sodium hydrogencarbonate solution was added over 40 min (foaming). 50 ml ethyl acetate were added. The mixture was stirred for 30 min at room temperature. The mixture was extracted with 200 ml and a second time with 50 ml ethyl acetate. The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution followed by 50 ml sat. aq. sodium chloride solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material). After 30 min at room temperature the reaction mixture was cooled to 0° C. The mixture was stirred for 30 min at room temperature The mixture was extracted with 200 ml The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution dried over sodium sulfate filtered concentrated under reduced pressure