2-cyclopropyl-3-oxobutanenitrile

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

Procedure: Into a 100-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of argon, was placed a solution of 2-cyclopropylacetonitrile (3.70 mL, 40.1 mmol) in THF (20 mL). The solution was cooled to −78° C., then LDA (2 M in THF, 30 mL, 60 mmol) was added drop-wise and the mixture was stirred for 1 h at −78° C. A solution of acetic anhydride (4.54 mL, 48.0 mmol) in tetrahydrofuran (10 mL) was added drop-wise at −78° C. The mixture was stirred for 1 h at 15° C., then carefully quenched with citric acid (10% aq, 200 mL). The mixture was extracted with diethyl ether (2×70 mL) and the combined organic extracts were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the title compound, which was used in the next step without purification. Into a 100-mL three neck round-bottom flask, which was purged maintained with an inert atmosphere of argon The mixture was stirred for 1 h at 15° C. carefully quenched with citric acid (10% aq, 200 mL) The mixture was extracted with diethyl ether (2×70 mL) the combined organic extracts were washed with brine (50 mL) dried (Na2SO4) filtered concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 250-mL round-bottom flask, was placed a solution of 2-cyclopropyl-3-oxobutanenitrile (compound 266.1, 4.0 g, 32.5 mmol) in ethanol (18 mL). AcOH (3 mL) and hydrazine hydrate (3.15 mL, 65 mmol) were added and the reaction was stirred overnight at 80° C. The reaction was cooled, then the pH was carefully adjusted to 9 with NaHCO3 (aq. sat.). The mixture was diluted with water, then extracted with ethyl acetate (6×60 mL) and the combined organic extracts were washed with brine (80 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the title compound as a brown oil (4.17 g, crude), which was used in the next step without purification. Into a 250-mL round-bottom flask, was placed The reaction was cooled extracted with ethyl acetate (6×60 mL) the combined organic extracts were washed with brine (80 mL) dried (Na2SO4) filtered concentrated under reduced pressure