N,N-diethyl-2-oxobutanamide

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

Procedure: To a suspension of 560.0 mg of compound (15) as obtained from example 9 (1.983 mmol) in 11.2 mL dimethoxyethane were added dropwise at 0° C. 1.68 mL concentrated aqueous hydrochloric acid (36.5%) (19.83 mmol, 10.0 eq). The ice bath was removed after 15 min and the triphasic mixture was vigorously stirred. After 4 h, the mixture was evaporated to dryness in a rotary evaporator (27° C., 5 mbar, then 1 mbar). The crude product was obtained as a lightly yellow semisolid (805.4mg, 194% by weight).333.3 mg crude product were purified by trituration with 0.7 mL methanol at room temperature for 18 h furnishing the title compound (168.7 mg, 0.425 mmol, 98% by weight) as white crystals. were added dropwise at 0° C The ice bath was removed after 15 min the mixture was evaporated to dryness in a rotary evaporator (27° C., 5 mbar The crude product was obtained as a lightly yellow semisolid (805.4mg, 194% by weight) 333.3 mg crude product were purified by trituration with 0.7 mL methanol at room temperature for 18 h

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: mL ethyl magnesium bromide solution (191.8 mmol, 1.10 eq) were diluted with 182.6 mL diethylether. The solution was cooled to −15° C. and a solution of 30.20 g of compound (8) as obtained from example 1 (174.4 mmol) in 60.4 mL diethylether was added dropwise. The resulting viscous suspension was stirred for additional 75 min at −15° C. Subsequently, the reaction was quenched by addition of 14.96 mL acetic acid (261.6 mmol, 1.5 eq). Then, 35 mL water were added to dissolve all salts and the cooling bath was removed. After 15 min, the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate and was filtered. The filter cake was washed with 40 mL diethylether. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 86° C. at 2.5 mbar) furnishing the title compound (18.66 g, 118.7 mmol, 68% by weight) as colorless liquid. was added dropwise to dissolve all salts the cooling bath was removed After 15 min the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate was filtered The filter cake was washed with 40 mL diethylether After evaporation of solvent in a rotary evaporator (40° C./10 mbar) the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid Purification a high vacuum distillation (bp 86° C. at 2.5 mbar)

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

Procedure: To a suspension of 560.0 mg of compound (15) as obtained from example 9 (1.983 mmol) in 11.2 mL dimethoxyethane were added dropwise at 0° C. 1.68 mL concentrated aqueous hydrochloric acid (36.5%) (19.83 mmol, 10.0 eq). The ice bath was removed after 15 min and the triphasic mixture was vigorously stirred. After 4 h, the mixture was evaporated to dryness in a rotary evaporator (27° C., 5 mbar, then 1 mbar). The crude product was obtained as a lightly yellow semisolid (805.4mg, 194% by weight).333.3 mg crude product were purified by trituration with 0.7 mL methanol at room temperature for 18 h furnishing the title compound (168.7 mg, 0.425 mmol, 98% by weight) as white crystals. were added dropwise at 0° C The ice bath was removed after 15 min the mixture was evaporated to dryness in a rotary evaporator (27° C., 5 mbar The crude product was obtained as a lightly yellow semisolid (805.4mg, 194% by weight) 333.3 mg crude product were purified by trituration with 0.7 mL methanol at room temperature for 18 h

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: mL ethyl magnesium bromide solution (191.8 mmol, 1.10 eq) were diluted with 182.6 mL diethylether. The solution was cooled to −15° C. and a solution of 30.20 g of compound (8) as obtained from example 1 (174.4 mmol) in 60.4 mL diethylether was added dropwise. The resulting viscous suspension was stirred for additional 75 min at −15° C. Subsequently, the reaction was quenched by addition of 14.96 mL acetic acid (261.6 mmol, 1.5 eq). Then, 35 mL water were added to dissolve all salts and the cooling bath was removed. After 15 min, the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate and was filtered. The filter cake was washed with 40 mL diethylether. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 86° C. at 2.5 mbar) furnishing the title compound (18.66 g, 118.7 mmol, 68% by weight) as colorless liquid. was added dropwise to dissolve all salts the cooling bath was removed After 15 min the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate was filtered The filter cake was washed with 40 mL diethylether After evaporation of solvent in a rotary evaporator (40° C./10 mbar) the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid Purification a high vacuum distillation (bp 86° C. at 2.5 mbar)

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

Procedure: To a suspension of 560.0 mg of compound (15) as obtained from example 9 (1.983 mmol) in 11.2 mL dimethoxyethane were added dropwise at 0° C. 1.68 mL concentrated aqueous hydrochloric acid (36.5%) (19.83 mmol, 10.0 eq). The ice bath was removed after 15 min and the triphasic mixture was vigorously stirred. After 4 h, the mixture was evaporated to dryness in a rotary evaporator (27° C., 5 mbar, then 1 mbar). The crude product was obtained as a lightly yellow semisolid (805.4mg, 194% by weight).333.3 mg crude product were purified by trituration with 0.7 mL methanol at room temperature for 18 h furnishing the title compound (168.7 mg, 0.425 mmol, 98% by weight) as white crystals. were added dropwise at 0° C The ice bath was removed after 15 min the mixture was evaporated to dryness in a rotary evaporator (27° C., 5 mbar The crude product was obtained as a lightly yellow semisolid (805.4mg, 194% by weight) 333.3 mg crude product were purified by trituration with 0.7 mL methanol at room temperature for 18 h

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: mL ethyl magnesium bromide solution (191.8 mmol, 1.10 eq) were diluted with 182.6 mL diethylether. The solution was cooled to −15° C. and a solution of 30.20 g of compound (8) as obtained from example 1 (174.4 mmol) in 60.4 mL diethylether was added dropwise. The resulting viscous suspension was stirred for additional 75 min at −15° C. Subsequently, the reaction was quenched by addition of 14.96 mL acetic acid (261.6 mmol, 1.5 eq). Then, 35 mL water were added to dissolve all salts and the cooling bath was removed. After 15 min, the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate and was filtered. The filter cake was washed with 40 mL diethylether. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 86° C. at 2.5 mbar) furnishing the title compound (18.66 g, 118.7 mmol, 68% by weight) as colorless liquid. was added dropwise to dissolve all salts the cooling bath was removed After 15 min the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate was filtered The filter cake was washed with 40 mL diethylether After evaporation of solvent in a rotary evaporator (40° C./10 mbar) the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid Purification a high vacuum distillation (bp 86° C. at 2.5 mbar)