4-bromo-2-ethenyl-1-fluorobenzene

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

Procedure: To a suspension of methyl(triphenyl)-phosphonium bromide (15.5 g, 43 mmol) in THF (60 ml) were added at −78° C. BuLi (27 ml, 1.6 M in hexane, 43.2 mmol) and 5-bromo-2-fluoro-benzaldehyde (877 mg, 43 mmol). The reaction mixture was stirred 18 hours at r.t. After work-up and purification by chromatography (hexane/ethyl acetate 9/1 to 4/1) 5.7 g (28.5 mmol, 72%) of the title compound were obtained, 1H-NMR (300 MHz, CDCl3): δ=7.62 (dd, 1H), 7.26-7.36 (m, 1H), 6.93 (t, 1H), 6.79 (dd, 1H), 5.42 (d, 1H). were added at −78° C

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

Procedure: To a suspension of methyl(triphenyl)-phosphonium bromide (15.5 g, 43 mmol) in THF (60 ml) were added at −78° C. BuLi (27 ml, 1.6 M in hexane, 43.2 mmol) and 5-bromo-2-fluoro-benzaldehyde (877 mg, 43 mmol). The reaction mixture was stirred 18 hours at r.t. After work-up and purification by chromatography (hexane/ethyl acetate 9/1 to 4/1) 5.7 g (28.5 mmol, 72%) of the title compound were obtained, 1H-NMR (300 MHz, CDCl3): δ=7.62 (dd, 1H), 7.26-7.36 (m, 1H), 6.93 (t, 1H), 6.79 (dd, 1H), 5.42 (d, 1H). were added at −78° C

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

Procedure: A mixture of methyltriphenylphosphonium bromide (2.14 g, 6 mmol) and potassium t-butoxide (672 mg, 6 mmol) in 50 mL of THF was refluxed for 30 minutes under N2 and then cooled to room temperature. 5-Bromo-2-fluorobenzaldehyde (1.02 g, 5 mmol) was added and the resulting mixture was refluxed for 2 hours (until the TLC showed the disappearance of starting aldehyde). The reaction was concentrated in vacuo and partitioned between water and ethyl acetate. The acetate layer was washed with water and brine. The solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether) to provide 900 mg (90%) of 5-bromo-2-fluorostyrene. was refluxed for 30 minutes under N2 the resulting mixture was refluxed for 2 hours (until the TLC The reaction was concentrated in vacuo partitioned between water and ethyl acetate The acetate layer was washed with water and brine The solution was dried over MgSO4 concentrated in vacuo The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether)

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

Procedure: The yellow oil from step A (2.8 g, 10 mmol) was dissolved in Ethyl acetate (200 mL). Palladium-on-carbon (10%, 250 mg) was added and the mixture was hydrogenated under 1 atmosphere until TLC showed complete reaction. The mixture was filtered and the filtrate was concentrated to give an oil. 2.4 g, 87%. reaction The mixture was filtered the filtrate was concentrated to give an oil

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

Procedure: 4-Bromo-1-fluoro-2-vinylbenzene (470 mg) was hydrogenated in EtOAc with 10% Pd/C (100 mg) with a hydrogen balloon for 2.0 h. The Pd/C was removed by filtration. The filtrate was condensed to give 95A (290 mg, 62% yield) as an orange oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.22 (t, J=6.81 Hz, 3H) 2.63 (d, J=7.03 Hz, 2H) 6.88 (t, J=8.57 Hz, 1H) 7.25 (s, 1H) 7.32 (d, J=4.39 Hz, 1H). The Pd/C was removed by filtration condensed

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

Procedure: A mixture of methyltriphenylphosphonium bromide (2.14 g, 6 mmol) and potassium t-butoxide (672 mg, 6 mmol) in 50 mL of THF was refluxed for 30 minutes under N2 and then cooled to room temperature. 5-Bromo-2-fluorobenzaldehyde (1.02 g, 5 mmol) was added and the resulting mixture was refluxed for 2 hours (until the TLC showed the disappearance of starting aldehyde). The reaction was concentrated in vacuo and partitioned between water and ethyl acetate. The acetate layer was washed with water and brine. The solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether) to provide 900 mg (90%) of 5-bromo-2-fluorostyrene. was refluxed for 30 minutes under N2 the resulting mixture was refluxed for 2 hours (until the TLC The reaction was concentrated in vacuo partitioned between water and ethyl acetate The acetate layer was washed with water and brine The solution was dried over MgSO4 concentrated in vacuo The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether)

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

Procedure: To a suspension of methyl(triphenyl)-phosphonium bromide (15.5 g, 43 mmol) in THF (60 ml) were added at −78° C. BuLi (27 ml, 1.6 M in hexane, 43.2 mmol) and 5-bromo-2-fluoro-benzaldehyde (877 mg, 43 mmol). The reaction mixture was stirred 18 hours at r.t. After work-up and purification by chromatography (hexane/ethyl acetate 9/1 to 4/1) 5.7 g (28.5 mmol, 72%) of the title compound were obtained, 1H-NMR (300 MHz, CDCl3): δ=7.62 (dd, 1H), 7.26-7.36 (m, 1H), 6.93 (t, 1H), 6.79 (dd, 1H), 5.42 (d, 1H). were added at −78° C

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

Procedure: A mixture of methyltriphenylphosphonium bromide (2.14 g, 6 mmol) and potassium t-butoxide (672 mg, 6 mmol) in 50 mL of THF was refluxed for 30 minutes under N2 and then cooled to room temperature. 5-Bromo-2-fluorobenzaldehyde (1.02 g, 5 mmol) was added and the resulting mixture was refluxed for 2 hours (until the TLC showed the disappearance of starting aldehyde). The reaction was concentrated in vacuo and partitioned between water and ethyl acetate. The acetate layer was washed with water and brine. The solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether) to provide 900 mg (90%) of 5-bromo-2-fluorostyrene. was refluxed for 30 minutes under N2 the resulting mixture was refluxed for 2 hours (until the TLC The reaction was concentrated in vacuo partitioned between water and ethyl acetate The acetate layer was washed with water and brine The solution was dried over MgSO4 concentrated in vacuo The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether)