ethyl 3-cyclopropyl-3-oxopropanoate

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:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (-70° C.) solution of monoethyl malonate (33.97 g, 257.10 mmol) in THF (639 mL) was added n-BuLi (1.6M in hexanes, 319 mL, 514.19 mmol) and the mixture was stirred under an argon atmosphere for 15 min. The resulting solution was cooled to -65° C. and cyclopropanecarbonyl chloride (15.55 g, 148.77 mmol) was added. The reaction mixture was stirred for 1 h and then allowed to warm up to room temperature. Some drops of water were added and THF was removed. The residue was taken up in 1N HCl/Et2O and extracted with Et2O. The organic phase was washed with saturated NaHCO3, dried and concentrated to a residue. This was purified by chromatography on silica gel (hexane-EtOAc mixtures of increasing polarity) to afford the title compound as a yellow oil (14.7 g, 63%). The reaction mixture was stirred for 1 h to warm up to room temperature THF was removed extracted with Et2O The organic phase was washed with saturated NaHCO3 dried concentrated to a residue This was purified by chromatography on silica gel (hexane-EtOAc mixtures of increasing polarity)

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

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

Procedure: 1.1 g of p-toluenesulphonic acid are added to 49.9 g (0.32 mol) of ethyl cyclopropylcarbonylacetate in 200 ml of dry toluene and the mixture is saturated with ammonia gas at room temperature with stirring. After allowing to stand overnight, the mixture is heated under reflux for 8 h in a water separator, ammonia gas being continuously introduced. The mixture is allowed to cool overnight and is filtered, and the toluene solution is concentrated in vacuo and distilled from unreacted starting material in a high vacuum up to 65° C. The substance is subsequently found in the residue. the mixture is heated continuously introduced to cool overnight is filtered the toluene solution is concentrated in vacuo distilled up to 65° C

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

Procedure: 1.1 g of p-toluenesulphonic acid are added to 49.9 g (0.32 mol) of ethyl cyclopropylcarbonylacetate in 200 ml of dry toluene and the mixture is saturated with ammonia gas at room temperature with stirring. After allowing to stand overnight, the mixture is boiled under reflux for 8 hours in a water separator, ammonia gas being continuously introduced. The mixture is allowed to cool overnight and is filtered, and the toluene solution is concentrated in vacuo and removed by distillation in a high vacuum up to 65° C. from unreacted starting material. The substance is subsequently found in the residue. Yield: 11.9 g (24% of theory). continuously introduced to cool overnight is filtered the toluene solution is concentrated in vacuo removed by distillation in a high vacuum up to 65° C.

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

Procedure: 1.1 g of p-toluenesulphonic acid are added to 49.9 g (0.32 mol) of ethyl cyclopropylcarbonylacetate in 200 ml of dry toluene and the mixture is saturated with ammonia gas at room temperature with stirring. After allowing to stand overnight, the mixture is boiled under reflux for 8 hours in a water separator, ammonia gas being continuously introduced. The mixture is allowed to cool overnight and is filtered, and the toluene solution is concentrated in vacuo and removed by distillation in a high vacuum up to 65° C. from unreacted starting material. The substance is subsequently found in the residue. Yield: 11.9 g (24% of theory). continuously introduced to cool overnight is filtered the toluene solution is concentrated in vacuo removed by distillation in a high vacuum up to 65° C.

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

Procedure: In analogy to the procedure described in Example 162A], 3-cyclopropyl-3-oxo-propionic acid ethyl ester and pyrimidine-5-carbonyl chloride gave the title compound as a yellow oil (40%). MS: 261.3 (M−H−).

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

Procedure: In analogy to the procedure described in Example 162A], 3-cyclopropyl-3-oxo-propionic acid ethyl ester and pyrimidine-5-carbonyl chloride gave the title compound as a yellow oil (40%). MS: 261.3 (M−H−).

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

Procedure: In analogy to the procedure described in Example 160A], 3-cyclopropyl-3-oxo-propionic acid ethyl ester and (1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetyl chloride gave the title compound as a white solid (60%). MS: 342.1 (M−H−).

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

Procedure: In analogy to the procedure described in Example 160A], 3-cyclopropyl-3-oxo-propionic acid ethyl ester and (1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetyl chloride gave the title compound as a white solid (60%). MS: 342.1 (M−H−).