(E)-4-amino-1,1,1-trifluorobut-3-en-2-one

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:0.00; pressure:0.00; stir:

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a three-necked flask, 61.6 g (0.55 mol) of potassium tert-butoxide were introduced into 250 ml of dimethoxyethane under N2 and the solution was cooled to 0° C. 4-Amino-1,1,1-trifluoro-3-buten-2-one, 69.5 g (0.5 mol), was added dropwise at this temperature in the course of 30 min and then 60.3 g (0.525 mol) of 3,3-dimethoxypropionitrile were added dropwise. The mixture was then stirred at 30° C. for 3-4 h. The reaction mixture was added to ice and acidified to pH 3-4 using HCl. The precipitate was filtered off and washed with water. The reaction mixture was added to ice The precipitate was filtered off washed with water

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

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

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

Procedure: Sodium hydride (60% dispersion in mineral oil, 0.6 g, 15 mmol) was charged and washed with hexane twice. Into this flask, 1,3-dimethyl-2-imidazolydinone (20 ml) was added and a solution prepared by dissolving 4-amino-1,1,1-trifluoro-3-buten-2-one (2.1 g, 15 mmol) and 3-methoxyacrylonitrile (1.2 g, 15 mmol) in 1,3-dimethyl-2-imidazolydinone (5 ml) was added dropwise under ice-cooling. After stirring the mixture at room temperature for 3 hours, the reaction mixture was poured into water (200 ml). This mixture was acidified with concentrated hydrochloric acid under ice-cooling and then extracted with ethyl acetate. The obtained organic layers were washed with saturated brine, dried over magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (a eluting solvent: hexane/ethyl acetate=3/1 to 2/1) to obtain 2.60 g (yield 92.0%) of a mixture of title compounds (IIa) and (IIb). washed with hexane twice Into this flask, 1,3-dimethyl-2-imidazolydinone (20 ml) was added a solution prepared was added dropwise under ice- cooling cooling extracted with ethyl acetate The obtained organic layers were washed with saturated brine dried over magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (a eluting solvent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Pentanone (1 ml, 9.4 mmol) was dissolved in 15 ml of dry toluene in a two-neck flask, and the solution was cooled to 0° C. under argon. LiHMDS (9.4 ml, 1.0 M in THF, 2.1 mmol) was added via syringe with stirring, and the formed anion was allowed to sit for 1 min before the addition of butyryl chloride (0.49 ml, 4.7 mmol) in one portion with stirring. The flask was then removed from ice bath and allowed to stand for 1 min, and 1M HCl solution was added with stirring. The solution mixture was extracted with EtOAc. The organic mixture was then washed with brine, dried over Na2SO4, and evaporated under reduced pressure. To a solution of the resulting crude residue in toluene (20 ml) was added 4-amino-1,1,1-trifluoro-3-butene-2-one (0.72 g, 4.7 mmol) and trifluoroacetic acid (0.42 ml, 5.64 mmol) and the mixture was stirred under reflux for 24 h. The reaction mixture was washed with aq. 20% Na2CO3 and dried with Na2SO4. After removal of the solvent, the residue was submitted to silica gel column chromatography to give a title compound (0.62 g, 51%). with stirring The flask was then removed from ice bath 1M HCl solution was added with stirring The solution mixture was extracted with EtOAc The organic mixture was then washed with brine dried over Na2SO4 evaporated under reduced pressure the mixture was stirred under reflux for 24 h The reaction mixture was washed with aq. 20% Na2CO3 dried with Na2SO4 After removal of the solvent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Pentanone (1 ml, 9.4 mmol) was dissolved in 15 ml of dry toluene in a two-neck flask, and the solution was cooled to 0° C. under argon. LiHMDS (9.4 ml, 1.0 M in THF, 2.1 mmol) was added via syringe with stirring, and the formed anion was allowed to sit for 1 min before the addition of butyryl chloride (0.49 ml, 4.7 mmol) in one portion with stirring. The flask was then removed from ice bath and allowed to stand for 1 min, and 1M HCl solution was added with stirring. The solution mixture was extracted with EtOAc. The organic mixture was then washed with brine, dried over Na2SO4, and evaporated under reduced pressure. To a solution of the resulting crude residue in toluene (20 ml) was added 4-amino-1,1,1-trifluoro-3-butene-2-one (0.72 g, 4.7 mmol) and trifluoroacetic acid (0.42 ml, 5.64 mmol) and the mixture was stirred under reflux for 24 h. The reaction mixture was washed with aq. 20% Na2CO3 and dried with Na2SO4. After removal of the solvent, the residue was submitted to silica gel column chromatography to give a title compound (0.62 g, 51%). with stirring The flask was then removed from ice bath 1M HCl solution was added with stirring The solution mixture was extracted with EtOAc The organic mixture was then washed with brine dried over Na2SO4 evaporated under reduced pressure the mixture was stirred under reflux for 24 h The reaction mixture was washed with aq. 20% Na2CO3 dried with Na2SO4 After removal of the solvent

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

Procedure: Sodium hydride (60% dispersion in mineral oil suspension, 4.00 g, 100 mmol) was added and washed with hexane twice. Into this flask, N,N-dimethylformamide (100 ml) was added and then a solution prepared by dissolving 4-amino-1,1,1-trifluoro-3-buten-2-one (13.9 g, 100 mmol) and 3-methoxyacrylonitrile (8.30 g, 100 mmol) in N,N-dimethylformamide (50 ml) was added dropwise under ice-cooling. After stirring the mixture at room temperature for 3 hours, the reaction mixture was poured into water (500 ml). This mixture was acidified with concentrated hydrochloric acid under ice-cooling, the precipitate was collected by filtration and then washed with cold water. The obtained precipitate was dried under reduced pressure to obtain 8.20 g (yield 43.1%) of a mixture of compounds (IIa) and (IIb). washed with hexane twice Into this flask, N,N-dimethylformamide (100 ml) was added a solution prepared was added dropwise under ice- cooling cooling the precipitate was collected by filtration washed with cold water The obtained precipitate was dried under reduced pressure