1-(4-bromo-2-fluorophenyl)propan-1-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:; See reaction.notes.procedure_details.

Procedure: Into a 1000-mL round-bottom flask, was placed a solution of 1-(4-bromo-2-fluorophenyl)propan-1-one (32 g, 138.53 mmol, 1.00 equiv) in ethanol (300 mL), 1-phenylhydrazine (15.0 g, 138.89 mmol, 1.00 equiv), TSA-H2O (1.32 g, 6.95 mmol, 0.05 equiv). The resulting solution was heated to reflux for 1 h in an oil bath. The resulting mixture was concentrated under vacuum to yield (Z)-1-(1-(4-bromo-2-fluorophenyl)propylidene)-2-phenylhydrazine and (E)-1-(1-(4-bromo-2-fluorophenyl)propylidene)-2-phenylhydrazine as a yellow solid. MS: 322 (MH+) Into a 1000-mL round-bottom flask, was placed The resulting solution was heated to reflux for 1 h in an oil bath The resulting mixture was concentrated under vacuum

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

Procedure: Into a 1000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-bromo-2-fluoro-N-methoxy-N-methylbenzamide (60 g, 229.01 mmol, 1.00 equiv) in tetrahydrofuran (200 mL). To the resulting mixture was then added ethylmagnesium bromide (2M) (185 mL, 1.60 equiv) dropwise with stirring at −20° C. The resulting solution was stirred for 2 h at room temperature, then cooled to 0° C. with a water/ice bath. The reaction was then quenched by the addition of NH4Cl/H2O (500 mL). The resulting solution was extracted with ethyl acetate (3×300 mL) and the organic layers combined. The resulting mixture was washed with water (1×300 mL) and brine (1×300 mL), then dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:20) to yield 1-(4-bromo-2-fluorophenyl)propan-1-one as a white solid. Into a 1000-mL 4-necked round-bottom flask purged maintained with an inert atmosphere of nitrogen cooled to 0° C. with a water/ice bath The reaction was then quenched by the addition of NH4Cl/H2O (500 mL) The resulting solution was extracted with ethyl acetate (3×300 mL) The resulting mixture was washed with water (1×300 mL) and brine (1×300 mL) dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-fluorobromobenzene (5.0 g, 29 mmol) and aluminium (III) chloride (11.6 g, 87 mmol) was heated under argon until a slurry formed. Propionyl chloride (3.2 g, 35 mmol) was added over 15 min and the mixture was heated at 90° C. for 1 h. The reaction was poured onto ice-water (100 mL) and the resultant mixture was extracted with dichloromethane (3×50 mL). The combined organic extracts were dried (magnesium sulfate), concentrated in vacuo and purified by column chromatography (SiO2; heptane) to give the product (1.2 g, 18%) as a colourless oil: NMR δH (400 MHz, CDCl3) 1.18 (3H, t, J 7.5), 2.95 (2H, m), 7.29-7.38 (2H, m) and 7.75 (1H, t, J 8 Hz). was heated under argon until a slurry formed The reaction was poured onto ice-water (100 mL) the resultant mixture was extracted with dichloromethane (3×50 mL) The combined organic extracts were dried (magnesium sulfate) concentrated in vacuo purified by column chromatography (SiO2; heptane)