1-(4-fluorophenyl)but-3-en-2-one

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

Procedure: To a solution of 104 mL (104.0 mmol, 1.2 equiv.) of a 1.0M solution of potassium tert-butoxide in THF and 100 mL dry THF under nitrogen atmosphere at −78° C. was added a solution of 14.2 g (86.6 mmol, 1 equiv.) of 1-(4-fluorophenyl)but-3-en-2-one (step B) and 13.0 g (86.6 mmol) tert-butylchlorodimethylsilane in 100 mL dry THF. The reaction mixture was stirred at −78° C. for 6 hr and at RT for 6 hr then quenched by the addition of 50 mL water. The resulting mixture was warmed to RT, diluted with 150 mL hexanes, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with 50 mL brine, dried over anhydrous magnesium sulfate, filtered and the solvent evaporated under vacuum to give 20.5 g of the crude title compounds which were used without further purification. 1H-NMR (CDCl3): δ: 7.52 (2H, m), 6.98 (2H, m), 6.33 (1H, dd, J1=13.2 Hz, J2=8.5 Hz), 5.97 (1H, s), 5.52 (1H, d, J=13.2 Hz), 5.17 (1H, d, J=8.5 Hz). then quenched by the addition of 50 mL water The resulting mixture was warmed to RT diluted with 150 mL hexanes transferred to a separatory funnel the organic layer separated The organic layer was washed with 50 mL brine dried over anhydrous magnesium sulfate filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 104 mL (104.0 mmol, 1.2 equiv.) of a 1.0M solution of potassium tert-butoxide in THF and 100 mL dry THF under nitrogen atmosphere at −78° C. was added a solution of 14.2 g (86.6 mmol, 1 equiv.) of 1-(4-fluorophenyl)but-3-en-2-one (step B) and 13.0 g (86.6 mmol) tert-butylchlorodimethylsilane in 100 mL dry THF. The reaction mixture was stirred at −78° C. for 6 hr and at RT for 6 hr then quenched by the addition of 50 mL water. The resulting mixture was warmed to RT, diluted with 150 mL hexanes, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with 50 mL brine, dried over anhydrous magnesium sulfate, filtered and the solvent evaporated under vacuum to give 20.5 g of the crude title compounds which were used without further purification. 1H-NMR (CDCl3): δ: 7.52 (2H, m), 6.98 (2H, m), 6.33 (1H, dd, J1=13.2 Hz, J2=8.5 Hz), 5.97 (1H, s), 5.52 (1H, d, J=13.2 Hz), 5.17 (1H, d, J=8.5 Hz). then quenched by the addition of 50 mL water The resulting mixture was warmed to RT diluted with 150 mL hexanes transferred to a separatory funnel the organic layer separated The organic layer was washed with 50 mL brine dried over anhydrous magnesium sulfate filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 220 mL (1.0 M, 220 mmol) of vinylmagnesium bromide in 100 mL THF, was added dropwise under nitrogen atmosphere at 0° C. a solution of 21 g (106.6 mmol) 2-(4-fluorophenyl)-N-methoxy-N-methylacetamide (step A) in ˜150 mL dry ether. The reaction mixture was stirred at 0° C. for 0.5 hr then poured slowly into an ice/2N aq HCl mixture. The resulting mixture was diluted with ether and brine, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with brine, dried over drying agent, filtered and the solvent evaporated under vacuum to give 14.2 g of the crude title compound which was used without further purification. 1H-NMR (CDCl3): δ: 7.19 (2H, m), 7.02 (2H, t, J=9.5 Hz), 6.42 (1H, dd, J=14.2 Hz, J2=11 Hz). 6.34 (1H, d, J=14.2 Hz), 5.86 (1H, d, J=11 Hz), 3.87 (2H, s). transferred to a separatory funnel the organic layer separated The organic layer was washed with brine dried over drying agent filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 220 mL (1.0 M, 220 mmol) of vinylmagnesium bromide in 100 mL THF, was added dropwise under nitrogen atmosphere at 0° C. a solution of 21 g (106.6 mmol) 2-(4-fluorophenyl)-N-methoxy-N-methylacetamide (step A) in ˜150 mL dry ether. The reaction mixture was stirred at 0° C. for 0.5 hr then poured slowly into an ice/2N aq HCl mixture. The resulting mixture was diluted with ether and brine, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with brine, dried over drying agent, filtered and the solvent evaporated under vacuum to give 14.2 g of the crude title compound which was used without further purification. 1H-NMR (CDCl3): δ: 7.19 (2H, m), 7.02 (2H, t, J=9.5 Hz), 6.42 (1H, dd, J=14.2 Hz, J2=11 Hz). 6.34 (1H, d, J=14.2 Hz), 5.86 (1H, d, J=11 Hz), 3.87 (2H, s). transferred to a separatory funnel the organic layer separated The organic layer was washed with brine dried over drying agent filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 104 mL (104.0 mmol, 1.2 equiv.) of a 1.0M solution of potassium tert-butoxide in THF and 100 mL dry THF under nitrogen atmosphere at −78° C. was added a solution of 14.2 g (86.6 mmol, 1 equiv.) of 1-(4-fluorophenyl)but-3-en-2-one (step B) and 13.0 g (86.6 mmol) tert-butylchlorodimethylsilane in 100 mL dry THF. The reaction mixture was stirred at −78° C. for 6 hr and at RT for 6 hr then quenched by the addition of 50 mL water. The resulting mixture was warmed to RT, diluted with 150 mL hexanes, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with 50 mL brine, dried over anhydrous magnesium sulfate, filtered and the solvent evaporated under vacuum to give 20.5 g of the crude title compounds which were used without further purification. 1H-NMR (CDCl3): δ: 7.52 (2H, m), 6.98 (2H, m), 6.33 (1H, dd, J3=13.2 Hz, J2=8.5 Hz), 5.97 (1H, s), 5.52 (1H, d, J=13.2 Hz), 5.17 (1H, d, J=8.5 Hz). then quenched by the addition of 50 mL water The resulting mixture was warmed to RT diluted with 150 mL hexanes transferred to a separatory funnel the organic layer separated The organic layer was washed with 50 mL brine dried over anhydrous magnesium sulfate filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 220 mL (1.0 M, 220 mmol) of vinylmagnesium bromide in 100 mL THF, was added dropwise under nitrogen atmosphere at 0° C. a solution of 21 g (106.6 mmol) 2-(4-fluoro-phenyl)-N-methoxy-N-methylacetamide (step A) in ˜150 mL dry ether. The reaction mixture was stirred at 0° C. for 0.5 hr then poured slowly into an ice/2N aq HCl mixture. The resulting mixture was diluted with ether and brine, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with brine, dried over drying agent, filtered and the solvent evaporated under vacuum to give 14.2 g of the crude title compound which was used without further purification. 1H-NMR (CDCl3): δ: 7.19 (2H, m), 7.02 (2H, t, J=9.5 Hz), 6.42 (1H, dd, J1=14.2 Hz, J2=11 Hz). 6.34 (1H, d, J=14.2 Hz), 5.86 (1H, d, J=11 Hz), 3.87 (2H, s). transferred to a separatory funnel the organic layer separated The organic layer was washed with brine dried over drying agent filtered the solvent evaporated under vacuum

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

Procedure: A solution of 21.5 g (131 mmol) of (E)-4-(4-fluorophenyl-but-3-en-2-one and 12 g (131 mmol) of glyoxylic acid monohydrate in 32 ml of acetic acid was heated at reflux for 20 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was extracted twice with 3N sodium hydroxide solution. The combined aqueous phases were treated with 3N hydrochloric acid to produce a strongly acidic reaction and extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated. Crystallization of the residue from ethyl acetate/ether yielded (E,E)-6-(4-fluorophenyl)-4-oxo-2,5-hexadienoic acid of melting point 160°-162°. at reflux for 20 hours extracted with ethyl acetate The organic phase was extracted twice with 3N sodium hydroxide solution The combined aqueous phases were treated with 3N hydrochloric acid to produce a strongly acidic reaction extracted twice with ethyl acetate The combined organic phases were dried over magnesium sulphate concentrated Crystallization of the residue from ethyl acetate/ether

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

Procedure: To a solution of 104 mL (104.0 mmol, 1.2 equiv.) of a 1.0M solution of potassium tert-butoxide in THF and 100 mL dry THF under nitrogen atmosphere at −78° C. was added a solution of 14.2 g (86.6 mmol, 1 equiv.) of 1-(4-fluorophenyl)but-3-en-2-one (step B) and 13.0 g (86.6 mmol) tert-butylchlorodimethylsilane in 100 mL dry THF. The reaction mixture was stirred at −78° C. for 6 hr and at RT for 6 hr then quenched by the addition of 50 mL water. The resulting mixture was warmed to RT, diluted with 150 mL hexanes, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with 50 mL brine, dried over anhydrous magnesium sulfate, filtered and the solvent evaporated under vacuum to give 20.5 g of the crude title compounds which were used without further purification. 1H-NMR (CDCl3): δ: 7.52 (2 H, m), 6.98 (2 H, m), 6.33 (1 H, dd, J1=13.2 Hz, J2=8.5 Hz), 5.97 (1 H, s), 5.52 (1 H, d, J=13.2 Hz), 5.17 (1 H, d, J=8.5 Hz). then quenched by the addition of 50 mL water The resulting mixture was warmed to RT diluted with 150 mL hexanes transferred to a separatory funnel the organic layer separated The organic layer was washed with 50 mL brine dried over anhydrous magnesium sulfate filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 220 mL (1.0 M, 220 mmol) of vinylmagnesium bromide in 100 mL THF, was added dropwise under nitrogen atmosphere at 0° C. a solution of 21 g (106.6 mmol) 2-(4-fluorophenyl)-N-methoxy-N-methylacetamide (step A) in ˜150 mL dry ether. The reaction mixture was stirred at 0° C. for 0.5 hr then poured slowly into an ice/2N aq HCl mixture. The resulting mixture was diluted with ether and brine, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with brine, dried over drying agent, filtered and the solvent evaporated under vacuum to give 14.2 g of the crude title compound which was used without further purification. 1H-NMR (CDCl3): δ: 7.19 (2 H, m), 7.02 (2 H, t, J=9.5 Hz), 6.42 (1 H, dd, J1=14.2 Hz, J2=11 Hz). 6.34 (1 H, d, J=14.2 Hz), 5.86 (1 H, d, J=11 Hz), 3.87 (2 H, s). transferred to a separatory funnel the organic layer separated The organic layer was washed with brine dried over drying agent filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 104 mL (104.0 mmol, 1.2 equiv.) of a 1.0M solution of potassium tert-butoxide in THF and 100 mL dry THF under nitrogen atmosphere at −78° C. was added a solution of 14.2 g (86.6 mmol, 1 equiv.) of 1-(4-fluorophenyl)but-3-en-2-one (step B) and 13.0 g (86.6 mmol)tert-butylchlorodimethylsilane in 100 mL dry THF. The reaction mixture was stirred at −78° C. for 6 hr and at RT for 6 hr then quenched by the addition of 50 mL water. The resulting mixture was warmed to RT, diluted with 150 mL hexanes, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with 50 mL brine, dried over anhydrous magnesium sulfate, filtered and the solvent evaporated under vacuum to give 20.5 g of the crude title compounds which were used without further purification. 1H-NMR (CDCl3): δ: 7.52 (2H, m), 6.98 (2H, m), 6.33 (1H, dd, J1=13.2 Hz, J2=8.5 Hz), 5.97 (1H, s), 5.52 (1H, d, J=13.2 Hz), 5.17 (1H, d, J=8.5 Hz). then quenched by the addition of 50 mL water The resulting mixture was warmed to RT diluted with 150 mL hexanes transferred to a separatory funnel the organic layer separated The organic layer was washed with 50 mL brine dried over anhydrous magnesium sulfate filtered the solvent evaporated under vacuum

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

Procedure: To a solution of 220 mL (1.0 M, 220mmol) of vinylmagnesium bromide in 100 mL THF, was added dropwise under nitrogen atmosphere at 0 ° C. a solution of 21 g (106.6 mmol) 2-(4-fluorophenyl)-N-methoxy-N-methylacetamide (step A) in ˜150 mL dry ether. The reaction mixture was stirred at 0° C. for 0.5 hr then poured slowly into an ice/2N aq HCl mixture. The resulting mixture was diluted with ether and brine, transferred to a separatory funnel and the organic layer separated. The organic layer was washed with brine, dried over drying agent, filtered and the solvent evaporated under vacuum to give 14.2 g of the crude title compound which was used without further purification. 1H-NMR (CDCl3): δ: 7.19 (2H, m), 7.02 (2H, t, J=9.5 Hz), 6.42 (1H, dd, J1=14.2Hz, J2=11Hz). 6.34 (1H, d, J=14.2Hz), 5.86 (1H, d, J=11 Hz), 3.87 (2H, s). transferred to a separatory funnel the organic layer separated The organic layer was washed with brine dried over drying agent filtered the solvent evaporated under vacuum