1-cyclopropylpropan-1-one

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

Procedure: Similarly to Example 3a), a solution of 4 g (40.8 mmol) of cyclopropyl ethyl ketone and 2.4 g (24 mmol) of methyl cyanoacetate was reacted to give 0.9 g (21% yield) of methyl 2-cyano-3-cyclopropylpent-2-enoate.

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

Procedure: Operations similar to Production Example 1-(1) were conducted using 1-cyclopropyl-1-propanone, and successively those of Production 1-(2) were conducted using 2-amino-5-nitropyridine. The solid whereupon obtained was suspended in ethyl acetate, washed with saturated aqueous sodium hydrogencarbonate solution and purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to provide the title compounds as yellow crystals. The solid whereupon obtained washed with saturated aqueous sodium hydrogencarbonate solution purified by silica gel column chromatography (hexane/ethyl acetate=4/1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 165 mL of an 1 M solution of bis(trimethylsilyl)lithiumamid in THF (166 mmol, 1.10 eq.) were brought forward in 500 mL of diethyl ether and cooled down to −78° C. 14.8 g of 1-cyclopropylpropan-1-one 1-12-1 was dissolved in 100 mL of diethyl ether and added dropwise at −78° C. The mixture was stirred for one hour at −78° C. and then 24.5 mL of diethyl oxalate was added dropwise. The cooling bath was removed and the mixture was stirred for 24 hours at rt. 500 mL of aqueous 1M hydrogen chloride solution was added and the mixture was extracted with DCM, dried over a silicone filter sulfate and concentrated in vacuo to provide 27.2 g (137 mmol, 91%) of the target compound as crude product. The crude product was used for the following step without further purification. added dropwise at −78° C The cooling bath was removed the mixture was stirred for 24 hours at rt 500 mL of aqueous 1M hydrogen chloride solution was added the mixture was extracted with DCM dried over a silicone filter sulfate concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 165 mL of an 1 M solution of bis(trimethylsilyl)lithiumamid in THF (166 mmol, 1.10 eq.) were brought forward in 500 mL of diethyl ether and cooled down to −78° C. 14.8 g of 1-cyclopropylpropan-1-one 1-12-1 was dissolved in 100 mL of diethyl ether and added dropwise at −78° C. The mixture was stirred for one hour at −78° C. and then 24.5 mL of diethyl oxalate was added dropwise. The cooling bath was removed and the mixture was stirred for 24 hours at rt. 500 mL of aqueous 1M hydrogen chloride solution was added and the mixture was extracted with DCM, dried over a silicone filter sulfate and concentrated in vacuo to provide 27.2 g (137 mmol, 91%) of the target compound as crude product. The crude product was used for the following step without further purification. added dropwise at −78° C The cooling bath was removed the mixture was stirred for 24 hours at rt 500 mL of aqueous 1M hydrogen chloride solution was added the mixture was extracted with DCM dried over a silicone filter sulfate concentrated in vacuo

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

Procedure: Similarly to Example 3a), a solution of 4 g (40.8 mmol) of cyclopropyl ethyl ketone and 2.4 g (24 mmol) of methyl cyanoacetate was reacted to give 0.9 g (21% yield) of methyl 2-cyano-3-cyclopropylpent-2-enoate.