1-HYDROXYMETHYL-CYCLOPROPANECARBOXYLIC ACID ETHYL ESTER

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of lithium aluminum-tri-tert-butoxyhydride 1.0M in THF (28.5 mL, 28.5 mmol) is added to a solution of diethyl 1,1-cyclopropanedicarboxylate (2.0 mL, 11.4 mmol) in anhydrous THF (85.0 mL). After stirring the reaction mixture for 4 h, 10 mL of lithium aluminum-tri-tert-butoxyhydride 1.0M solution in THF is added and the solution is stirred for 18 h. The reaction mixture is diluted with DCM, washed with 1N aqueous HCl solution, saturated aqueous NaHCO3 solution and brine. After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressure affords 1.60 g of 1-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester that is used in the next step without further purification. Yield: 85%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.88 (2H, q, J=4.1 Hz), 1.21-1.33 (5H, m), 2.59 (1H, t, J=6.9 Hz), 3.63 (2H, d, J=7.2 Hz), 4.17 (2H, q, J=7.1 Hz). the solution is stirred for 18 h washed with 1N aqueous HCl solution, saturated aqueous NaHCO3 solution and brine After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressure

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

実験手順: At 0° C., 5.05 g (11.9 mmol) of Dess-Martin periodane reagent were added to a solution of 1.225 g (8.5 mmol) of ethyl 1-hydroxymethylcyclopropanecarboxylate [for the preparation see, for example, T. A. Ayers, Tetrahedron Lett. 40 (30), 5467-5470 (1999)] in 43 ml of dichloromethane, and the mixture was then stirred at RT for 6 h. A solution of 6.7 g (42.5 mmol) of sodium thiosulfate in 60 ml of saturated aqueous sodium bicarbonate solution was then added to the reaction mixture. The mixture was stirred at RT for 20 min, and the phases were then separated. The organic phase was washed twice with water, dried over magnesium sulfate and concentrated at 20° C. under reduced pressure. This gave 1.139 g (80.0% of theory) of the target compound. the phases were then separated The organic phase was washed twice with water dried over magnesium sulfate concentrated at 20° C. under reduced pressure

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

実験手順: A solution of lithium aluminum-tri-tert-butoxyhydride 1.0M in THF (28.5 mL, 28.5 mmol) is added to a solution of diethyl 1,1-cyclopropanedicarboxylate (2.0 mL, 11.4 mmol) in anhydrous THF (85.0 mL). After stirring the reaction mixture for 4 h, 10 mL of lithium aluminum-tri-tert-butoxyhydride 1.0M solution in THF is added and the solution is stirred overnight. The reaction mixture is diluted with DCM, washed with 1N HCl, saturated NaHCO3 solution and brine. After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressure affords 1.60 g of 1-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester that is used in the next step without further purification. Yield: 85%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.88 (2H, q, J=4.1 Hz), 1.21-1.33 (5H, m), 2.59 (1H, t, J=6.9 Hz), 3.63 (2H, d, J=7.2 Hz), 4.17 (2H, q, J=7.1 Hz). the solution is stirred overnight washed with 1N HCl, saturated NaHCO3 solution and brine After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressure

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

実験手順: To a solution of Preparation 232 1-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester (3.00 g, 21.00 mmol) in dichloromethane (50 ml), at 0° C., was added saturated sodium hydrogen carbonate solution (50 ml), followed by TEMPO (659 mg, 4.00 mmol) and sodium bromide (400 mg, 4.00 mmol). After stirring for 5 min, sodium hypochlorite solution (10%, 14.00 mmol) was added slowly, followed by saturated sodium thiosulphate solution (50 ml). The two layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic phases were dried (MgSO4) and concentrated in vacuo to give the titled compound (3.00 g). The two layers were separated the aqueous layer was extracted with dichloromethane The combined organic phases were dried (MgSO4) concentrated in vacuo

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

実験手順: A solution of lithium aluminum-tri-tert-butoxyhydride 1.0M in THF (28.5 mL, 28.5 mmol) is added to a solution of diethyl 1,1-cyclopropanedicarboxylate (2.0 mL, 11.4 mmol) in anhydrous THF (85.0 mL). After stirring the reaction mixture for 4 h, 10 mL of lithium aluminum-tri-tert-butoxyhydride 1.0M solution in THF is added and the solution is stirred for 18 h. The reaction mixture is diluted with DCM, washed with 1N aqueous HCl solution, saturated aqueous NaHCO3 solution and brine. After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressure affords 1.60 g of 1-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester that is used in the next step without further purification. Yield: 85%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.88 (2H, q, J=4.1 Hz), 1.21-1.33 (5H, m), 2.59 (1H, t, J=6.9 Hz), 3.63 (2H, d, J=7.2 Hz), 4.17 (2H, q, J=7.1 Hz). the solution is stirred for 18 h washed with 1N aqueous HCl solution, saturated aqueous NaHCO3 solution and brine After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressure

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

実験手順: At 0° C., 5.05 g (11.9 mmol) of Dess-Martin periodane reagent were added to a solution of 1.225 g (8.5 mmol) of ethyl 1-hydroxymethylcyclopropanecarboxylate [for the preparation see, for example, T. A. Ayers, Tetrahedron Lett. 40 (30), 5467-5470 (1999)] in 43 ml of dichloromethane, and the mixture was then stirred at RT for 6 h. A solution of 6.7 g (42.5 mmol) of sodium thiosulfate in 60 ml of saturated aqueous sodium bicarbonate solution was then added to the reaction mixture. The mixture was stirred at RT for 20 min, and the phases were then separated. The organic phase was washed twice with water, dried over magnesium sulfate and concentrated at 20° C. under reduced pressure. This gave 1.139 g (80.0% of theory) of the target compound. the phases were then separated The organic phase was washed twice with water dried over magnesium sulfate concentrated at 20° C. under reduced pressure

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

実験手順: In accordance with the method described in the document (Tetrahedron Letters, 40, 5467 (1988)), a solution of 720 mg of 1-hydroxymethyl-cyclopropane carboxylic acid ethyl ester obtained from 1,1-cyclopropane dicarboxylic acid diethyl ester in 10 mL of dichloromethane was added with 1.05 mL of triethylamine and 0.5 mL of methanesulfonyl chloride under ice cooling, and stirred at this temperature for 2 hours. After adding water, the reaction solution was extracted with ethyl acetate. The organic layer was washed successively with 1N hydrochloric acid, saturated brine, saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, to afford 1.04 g of the title compound as a pale yellow oil.

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: In accordance with the method described in the document (Tetrahedron Letters, 40, 5467 (1988)), a solution of 720 mg of 1-hydroxymethyl-cyclopropane carboxylic acid ethyl ester obtained from 1,1-cyclopropane dicarboxylic acid diethyl ester in 10 mL of dichloromethane was added with 1.05 mL of triethylamine and 0.5 mL of methanesulfonyl chloride under ice cooling, and stirred at this temperature for 2 hours. After adding water, the reaction solution was extracted with ethyl acetate. The organic layer was washed successively with 1N hydrochloric acid, saturated brine, saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, to afford 1.04 g of the title compound as a pale yellow oil.

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

実験手順: To a solution of Preparation 232 1-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester (3.00 g, 21.00 mmol) in dichloromethane (50 ml), at 0° C., was added saturated sodium hydrogen carbonate solution (50 ml), followed by TEMPO (659 mg, 4.00 mmol) and sodium bromide (400 mg, 4.00 mmol). After stirring for 5 min, sodium hypochlorite solution (10%, 14.00 mmol) was added slowly, followed by saturated sodium thiosulphate solution (50 ml). The two layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic phases were dried (MgSO4) and concentrated in vacuo to give the titled compound (3.00 g). The two layers were separated the aqueous layer was extracted with dichloromethane The combined organic phases were dried (MgSO4) 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 Preparation 232 1-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester (3.00 g, 21.00 mmol) in dichloromethane (50 ml), at 0° C., was added saturated sodium hydrogen carbonate solution (50 ml), followed by TEMPO (659 mg, 4.00 mmol) and sodium bromide (400 mg, 4.00 mmol). After stirring for 5 min, sodium hypochlorite solution (10%, 14.00 mmol) was added slowly, followed by saturated sodium thiosulphate solution (50 ml). The two layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic phases were dried (MgSO4) and concentrated in vacuo to give the titled compound (3.00 g). The two layers were separated the aqueous layer was extracted with dichloromethane The combined organic phases were dried (MgSO4) concentrated in vacuo