methyl 3-cyclobutyl-3-oxopropanoate

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

Procedure: 22 g of meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (152.7 mmol) and 36.9 ml of pyridine (457.2 mmol) were dissolved in 200 ml of dichloromethane. 18.1 g of cyclobutylcarbonic acid chloride were added at 0 to 10° C. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCl and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and heated under reflux for 2 h. The reaction mixture was concentrated to dryness and the residue purified via silica gel chromatography with ethyl acetate as eluent. Yield: 21.2 g washed with 1 N HCl extracted with dichloromethane The organic layer was washed with water dried over magnesium sulfate filtered concentrated to dryness The oily residue was dissolved in 300 ml of methanol heated under reflux for 2 h The reaction mixture was concentrated to dryness the residue purified via silica gel chromatography with ethyl acetate as eluent

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

Procedure: A mixture of methyl 3-cyclobutyl-3-oxo-propanoate (4.3 g, 27.53 mmol) and 2,2-dimethylpropanamidine (2.3 g, 22.10 mmol) was stirred in dry MeOH (50 mL) and NaOMe (5.0 g, 92 mmol) was added in portions at 10° C. The suspension was stirred at room temperature overnight. The reaction mixture was concentrated to roughly half of the volume and filtered. The filtrate was extracted with water and DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was stirred with acetone and the precipitate collected, dried under vacuum to give the title compound (3.15 g, 15.27 mmol, 66%). The reaction mixture was concentrated to roughly half of the volume filtered The filtrate was extracted with water and DCM The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The residue was stirred with acetone the precipitate collected dried under vacuum

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

Procedure: A mixture of methyl 3-cyclobutyl-3-oxo-propanoate (4.3 g, 27.53 mmol) and 2,2-dimethylpropanamidine (2.3 g, 22.10 mmol) was stirred in dry MeOH (50 mL) and NaOMe (5.0 g, 92 mmol) was added in portions at 10° C. The suspension was stirred at room temperature overnight. The reaction mixture was concentrated to roughly half of the volume and filtered. The filtrate was extracted with water and DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was stirred with acetone and the precipitate collected, dried under vacuum to give the title compound (3.15 g, 15.27 mmol, 66%). The reaction mixture was concentrated to roughly half of the volume filtered The filtrate was extracted with water and DCM The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The residue was stirred with acetone the precipitate collected dried under vacuum

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

Procedure: 22 g of meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (152.7 mmol) and 36.9 ml of pyridine (457.2 mmol) were dissolved in 200 ml of dichloromethane. 18.1 g of cyclobutylcarbonic acid chloride were added at 0 to 10° C. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCl and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and heated under reflux for 2 h. The reaction mixture was concentrated to dryness and the residue purified via silica gel chromatography with ethyl acetate as eluent. Yield: 21.2 g washed with 1 N HCl extracted with dichloromethane The organic layer was washed with water dried over magnesium sulfate filtered concentrated to dryness The oily residue was dissolved in 300 ml of methanol heated under reflux for 2 h The reaction mixture was concentrated to dryness the residue purified via silica gel chromatography with ethyl acetate as eluent

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

Procedure: 22 g of meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (152.7 mmol) and 36.9 ml of pyridine (457.2 mmol) were dissolved in 200 ml of dichloromethane. 18.1 g of cyclobutylcarbonic acid chloride were added at 0 to 10° C. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCl and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and heated under reflux for 2 h. The reaction mixture was concentrated to dryness and the residue purified via silica gel chromatography with ethyl acetate as eluent. Yield: 21.2 g washed with 1 N HCl extracted with dichloromethane The organic layer was washed with water dried over magnesium sulfate filtered concentrated to dryness The oily residue was dissolved in 300 ml of methanol heated under reflux for 2 h The reaction mixture was concentrated to dryness the residue purified via silica gel chromatography with ethyl acetate as eluent

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

Procedure: 22 g of meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (152.7 mmol) and 36.9 ml of pyridine (457.2 mmol) were dissolved in 200 ml of dichloromethane. 18.1 g of cyclobutylcarbonic acid chloride were added at 0 to 10° C. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCl and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and heated under reflux for 2 h. The reaction mixture was concentrated to dryness and the residue purified via silica gel chromatography with ethyl acetate as eluent. Yield: 21.2 g washed with 1 N HCl extracted with dichloromethane The organic layer was washed with water dried over magnesium sulfate filtered concentrated to dryness The oily residue was dissolved in 300 ml of methanol heated under reflux for 2 h The reaction mixture was concentrated to dryness the residue purified via silica gel chromatography with ethyl acetate as eluent

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

Procedure: A mixture of methyl 3-cyclobutyl-3-oxo-propanoate (4.3 g, 27.53 mmol) and 2,2-dimethylpropanamidine (2.3 g, 22.10 mmol) was stirred in dry MeOH (50 mL) and NaOMe (5.0 g, 92 mmol) was added in portions at 10° C. The suspension was stirred at room temperature overnight. The reaction mixture was concentrated to roughly half of the volume and filtered. The filtrate was extracted with water and DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was stirred with acetone and the precipitate collected, dried under vacuum to give the title compound (3.15 g, 15.27 mmol, 66%). The reaction mixture was concentrated to roughly half of the volume filtered The filtrate was extracted with water and DCM The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The residue was stirred with acetone the precipitate collected dried under vacuum

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

Procedure: A mixture of methyl 3-cyclobutyl-3-oxo-propanoate (4.3 g, 27.53 mmol) and 2,2-dimethylpropanamidine (2.3 g, 22.10 mmol) was stirred in dry MeOH (50 mL) and NaOMe (5.0 g, 92 mmol) was added in portions at 10° C. The suspension was stirred at room temperature overnight. The reaction mixture was concentrated to roughly half of the volume and filtered. The filtrate was extracted with water and DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was stirred with acetone and the precipitate collected, dried under vacuum to give the title compound (3.15 g, 15.27 mmol, 66%). The reaction mixture was concentrated to roughly half of the volume filtered The filtrate was extracted with water and DCM The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The residue was stirred with acetone the precipitate collected dried under vacuum

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

Procedure: 22 g of meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (152.7 mmol) and 36.9 ml of pyridine (457.2 mmol) were dissolved in 200 ml of dichloromethane. 18.1 g of cyclobutylcarbonic acid chloride were added at 0 to 10° C. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCl and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and heated under reflux for 2 h. The reaction mixture was concentrated to dryness and the residue purified via silica gel chromatography with ethyl acetate as eluent. Yield: 21.2 g washed with 1 N HCl extracted with dichloromethane The organic layer was washed with water dried over magnesium sulfate filtered concentrated to dryness The oily residue was dissolved in 300 ml of methanol heated under reflux for 2 h The reaction mixture was concentrated to dryness the residue purified via silica gel chromatography with ethyl acetate as eluent

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

Procedure: 22 g of meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (152.7 mmol) and 36.9 ml of pyridine (457.2 mmol) were dissolved in 200 ml of dichloromethane. 18.1 g of cyclobutylcarbonic acid chloride were added at 0 to 10° C. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCl and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and heated under reflux for 2 h. The reaction mixture was concentrated to dryness and the residue purified via silica gel chromatography with ethyl acetate as eluent. Yield: 21.2 g washed with 1 N HCl extracted with dichloromethane The organic layer was washed with water dried over magnesium sulfate filtered concentrated to dryness The oily residue was dissolved in 300 ml of methanol heated under reflux for 2 h The reaction mixture was concentrated to dryness the residue purified via silica gel chromatography with ethyl acetate as eluent