1-bromo-4-prop-1-ynylbenzene

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

Procedure: To a solution of 1-bromo-4-ethynyl-benzene (500 mg, 2.8 mmol) in tetrahydrofuran (20 mL) at −30° C. was slowly added sodium bis(trimethylsilyl)amide in tetrahydrofuran solution (1M, 4.2 mL). After stirring 15 min, methyl iodide (1.1 g, 8.4 mmol) was added at −20° C. The resulting reaction mixture was stirred at RT for 50 min before it was added to water. The mixture was extracted with ethyl acetate and the organic phase was dried over magnesium sulfate and concentrated. The crude product 1-bromo-4-prop-1-ynyl-benzene was obtained as a volatile liquid (450 mg, 82.8% yield) which was put to next step directly without further purification. 1H NMR (400 MHz, MeOD) δ ppm 7.34 (d, J=8.3 Hz, 10H), 7.14 (d, J=8.3 Hz, 10H), 1.91 (s, 3H); GCMS, (M+1)=195.1, Molecular Formula=C9H7Br. at −30° C. The resulting reaction mixture was stirred at RT for 50 min before it The mixture was extracted with ethyl acetate the organic phase was dried over magnesium sulfate concentrated

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

Procedure: A solution of 1 g of 1-(1-propynyl)-4-bromo-benzene (produced from 4-bromobenzaldehyde by Wittig reaction, bromination of the resulting ethane and bromine elimination analogously to Example 1e) is reacted with 700 mg of tetrakis(triphenylphosphine)palladium (0) and 1.53 g of 4-(4-pentylphenyl)-2,3-difluoro-benzeneboric acid as described under a). Chromatography on silica gel with 3% ethyl acetate in petroleum ether and fractional crystallization from ethyl acetate gives 0.84 g of 1-(4-pentylphenyl)-2,3-difluoro-4-[4-(1-propynyl)-phenyl]benzene, m.p. 102.9° C.; cl.p. (N-I) 198.9° C.

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

Procedure: Into a 250-mL three neck round-bottom flask, which was maintained with an inert atmosphere of nitrogen, was placed 1-bromo-4-iodobenzene (2.00 g, 7.07 mmol), PdCl2(PPh3)2 (99.2 mg, 0.14 mmol), CuI (26.8 mg, 0.14 mmol), trimethyl(prop-1-yn-1-yl)silane (2.08 mL, 14.1 mmol) and tetrahydrofuran/TEA (9:1) (100 mL). Stirring was initiated and tetrabutylammonium fluoride (3.69 g, 14.1 mmol) was added rapidly to the mixture. The resulting mixture was stirred for 18 h at room temperature, then concentrated under reduced pressure. The residue diluted with water (100 mL) and extracted with ethyl acetate (3×50 mL). The organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with petroleum ether as the eluent to yield the title compound as a light yellow oil (1.0 g, 73%). The resulting mixture was stirred for 18 h at room temperature concentrated under reduced pressure The residue diluted with water (100 mL) extracted with ethyl acetate (3×50 mL) The organic extracts were dried (Na2SO4) filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography with petroleum ether as the eluent