ethyl 1-methylcyclopropane-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:; See reaction.notes.procedure_details.

実験手順: 0.48 g (20 mmoles) of sodium is dissolved in 20 ml of anhydrous ethanol. This solution is added to an ethanol solution containing 2.48 g (10 mmoles) of N-[imino(cyclopropylamino)methyl]-4-morpholinecarboximidamide hydrochloride, and 2.82 g (22 mmoles) of ethyl 1-methylcyclopropane-carboxylate are then also added to the mixture. The mixture is then heated under reflux under nitrogen for 88 hours. It is cooled, the alcohol is evaporated under reduced pressure and the residue is redissolved in 50 ml of water and 200 ml of dichloromethane. The aqueous phase is separated off and the organic phase is washed twice with 50 ml of water and dried over magnesium sulfate. The solvent is evaporated under reduced pressure and the residue is recrystallized from a 1:1 (v/v) mixture of petroleum ether-dichloromethane. 0.49 g of 2-cyclopropylamino-4-(1-methylcyclopropyl)-6-morpholino-1,3,5-triazine is obtained. Yield: 17%. M.P.: 94°-95°% C. are then also added to the mixture The mixture is then heated under reflux under nitrogen for 88 hours It is cooled the alcohol is evaporated under reduced pressure the residue is redissolved in 50 ml of water The aqueous phase is separated off the organic phase is washed twice with 50 ml of water dried over magnesium sulfate The solvent is evaporated under reduced pressure the residue is recrystallized from a 1:1 (v/v) mixture of petroleum ether-dichloromethane

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

実験手順: 0.48 g (20 mmoles) of sodium is dissolved in 20 ml of anhydrous ethanol. This solution is added to an ethanol solution containing 2.48 g (10 mmoles) of N-[imino(cyclopropylamino)methyl]-4-morpholinecarboximidamide hydrochloride, and 2.82 g (22 mmoles) of ethyl 1-methylcyclopropane-carboxylate are then also added to the mixture. The mixture is then heated under reflux under nitrogen for 88 hours. It is cooled, the alcohol is evaporated under reduced pressure and the residue is redissolved in 50 ml of water and 200 ml of dichloromethane. The aqueous phase is separated off and the organic phase is washed twice with 50 ml of water and dried over magnesium sulfate. The solvent is evaporated under reduced pressure and the residue is recrystallized from a 1:1 (v/v) mixture of petroleum ether-dichloromethane. 0.49 g of 2-cyclopropylamino-4-(1-methylcyclopropyl)-6-morpholino-1,3,5-triazine is obtained. Yield: 17%. M.P.: 94°-95°% C. are then also added to the mixture The mixture is then heated under reflux under nitrogen for 88 hours It is cooled the alcohol is evaporated under reduced pressure the residue is redissolved in 50 ml of water The aqueous phase is separated off the organic phase is washed twice with 50 ml of water dried over magnesium sulfate The solvent is evaporated under reduced pressure the residue is recrystallized from a 1:1 (v/v) mixture of petroleum ether-dichloromethane

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

実験手順: Alternatively, to a 5 L three-necked round-bottom flask equipped with overhead stirrer, thermocouple, reflux condenser, and an addition funnel, add potassium tert-butoxide in THF (3.00 L, 3.00 moles). Mix 1-methyl-cyclopropanecarboxylic acid ethyl ester (264.00 g, 2.06 moles) with acetonitrile (123.00 g, 3.00 moles), then add through an addition funnel over 0.5 hour to the butoxide solution. Heat the resulting mixture to reflux. Reflux 2 hours, then cool to <40° C. by adding methanol (96.00 g, 3.00 mL). Stir the mixture 10 minutes, then transfer the contents to a 12 L separatory funnel containing a vigorously stirring mixture of water (3.96 L, 219.81 moles) and MTBE (3.96 L, 33.32 moles). Separate the layers and extract the aqueous layer with MTBE (3.96 L, 33.32 moles). Adjust the pH of the aqueous layer from 12.5 to 3.5 using 5 N HCl (610.00 mL, 3.05 moles). Extract the aqueous layer with MTBE (2×1.32 L, 11.11). Combine the organic layers, dry over sodium sulfate (62.00 g, 436.49 moles), and filter to afford 3-(1-methyl-cyclopropyl)-3-oxo-propionitrile. Alternatively, to a 5 L three-necked round-bottom flask equipped with overhead stirrer thermocouple, reflux condenser, and an addition funnel Heat the resulting mixture to reflux Reflux 2 hours cool to <40° C. containing a vigorously stirring Separate the layers Extract the aqueous layer with MTBE (2×1.32 L, 11.11) filter

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

実験手順: Alternatively, to a 5 L three-necked round-bottom flask equipped with overhead stirrer, thermocouple, reflux condenser, and an addition funnel, add potassium tert-butoxide in THF (3.00 L, 3.00 moles). Mix 1-methyl-cyclopropanecarboxylic acid ethyl ester (264.00 g, 2.06 moles) with acetonitrile (123.00 g, 3.00 moles), then add through an addition funnel over 0.5 hour to the butoxide solution. Heat the resulting mixture to reflux. Reflux 2 hours, then cool to <40° C. by adding methanol (96.00 g, 3.00 mL). Stir the mixture 10 minutes, then transfer the contents to a 12 L separatory funnel containing a vigorously stirring mixture of water (3.96 L, 219.81 moles) and MTBE (3.96 L, 33.32 moles). Separate the layers and extract the aqueous layer with MTBE (3.96 L, 33.32 moles). Adjust the pH of the aqueous layer from 12.5 to 3.5 using 5 N HCl (610.00 mL, 3.05 moles). Extract the aqueous layer with MTBE (2×1.32 L, 11.11). Combine the organic layers, dry over sodium sulfate (62.00 g, 436.49 moles), and filter to afford 3-(1-methyl-cyclopropyl)-3-oxo-propionitrile. Alternatively, to a 5 L three-necked round-bottom flask equipped with overhead stirrer thermocouple, reflux condenser, and an addition funnel Heat the resulting mixture to reflux Reflux 2 hours cool to <40° C. containing a vigorously stirring Separate the layers Extract the aqueous layer with MTBE (2×1.32 L, 11.11) filter

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

実験手順: 0.48 g (20 mmoles) of sodium is dissolved in 20 ml of anhydrous ethanol. This solution is added to an ethanol solution containing 2.48 g (10 mmoles) of N-[imino(cyclopropylamino)methyl]-4-morpholinecarboximidamide hydrochloride, and 2.82 g (22 mmoles) of ethyl 1-methylcyclopropane-carboxylate are then also added to the mixture. The mixture is then heated under reflux under nitrogen for 88 hours. It is cooled, the alcohol is evaporated under reduced pressure and the residue is redissolved in 50 ml of water and 200 ml of dichloromethane. The aqueous phase is separated off and the organic phase is washed twice with 50 ml of water and dried over magnesium sulfate. The solvent is evaporated under reduced pressure and the residue is recrystallized from a 1:1 (v/v) mixture of petroleum ether-dichloromethane. 0.49 g of 2-cyclopropylamino-4-(1-methylcyclopropyl)-6-morpholino-1,3,5-triazine is obtained. Yield: 17%. M.P.: 94°-95°% C. are then also added to the mixture The mixture is then heated under reflux under nitrogen for 88 hours It is cooled the alcohol is evaporated under reduced pressure the residue is redissolved in 50 ml of water The aqueous phase is separated off the organic phase is washed twice with 50 ml of water dried over magnesium sulfate The solvent is evaporated under reduced pressure the residue is recrystallized from a 1:1 (v/v) mixture of petroleum ether-dichloromethane

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: 100 gm of 1-methylcyclopropanoic acid was added to 150 ml of diethyl ether. The system was cooled to 0°-5° C. and 119 gm of thionyl chloride was added dropwise over a period of time. After addition, the system was heated at reflux for 8 hours. The system was then cooled to 0°-5° C. and 62 gm of ethanethiol was added dropwise. The system was heated at reflux for 6 hours and then stirred at room temperature for 72 hours. The diethyl ether was removed by stripping to give the 1-methylcyclopropanoic acid ethyl ester. The system was cooled to 0°-5° C. After addition the system was heated at reflux for 8 hours The system was then cooled to 0°-5° C. The system was heated at reflux for 6 hours The diethyl ether was removed

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

実験手順: 100 g of 1-methylcyclopropanoic acid was added to 150 ml of diethyl ether. The system was cooled to 0°-5° C. and 119 gm of thionyl chloride was added dropwise over a period of time. After addition, the system was heated at reflux for 8 hours. The system was then cooled to 0°-5° C. and 62 gm of ethanethiol was added dropwise. The system was heated at reflux for 6 hours and then stirred at room temperature for 72 hours. The diethyl ether was removed by stripping to give the 1-methylcyclopropanoic acid ethyl ester. The system was cooled to 0°-5° C. After addition the system was heated at reflux for 8 hours The system was then cooled to 0°-5° C. The system was heated at reflux for 6 hours The diethyl ether was removed

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

実験手順: Cannon and coworkers (J. Am. Chem. Soc., 1959, 81, pages 1660-1666) disclose the reaction of α-methyl-γ-chlorobutyric acid ethyl ester with sodamide under strictly anhydrous conditions in benzene to provide 1-methylcyclopropane carboxylic acid ethyl ester in a yield of 47.6%. Schwarze and coworkers, U.S. Pat. No. 4,520,209, disclose the reaction of methyl 4-chloro-2-methylbutyrate in methanol with an excess of sodium methylate at a reaction temperature of 90° C. or higher. Although, an 87% yield was claimed by Schwarze et al., wiped film distillation or extraction was required to the separate methyl 1-methylcyclopropanecarboxylate from the sodium chloride by-product. Schwarze and coworkers disclose a boiling point for methyl 1-methylcyclopropanecarboxylate of 136° C. German Patent Publication DE 3026094 discloses the conversion of 4-chloro-2-methylbutyrate to 1-methylcyclopropaneamide via sodium methoxide/ammonia in an autoclave at 145° C.