1,3-dibromo-2-methylbenzene

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:0.00; 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:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,6-dibromotoluene (22.9 g, 92 mmol), N-bromosuccinimide (NBS) (15 g, 84 mmol), CCl4 (250 mL) and benzoyl peroxide (0.03 eq) was stirred at 85° C. (hot oil bath temperature) for 16 h, cooled to RT, filtered, washed with aq. NaHSO3, dried (Na2SO4), filtered, and evaporated to give 29.5 g (yield of 98%) of title product as a white solid. This solid contained 10% unreacted starting material but was successfully used without further purification. 1H NMR (300 MHz, CDCl3) δ 4.81 (s, 2H), 7.01 (t, 1H), 7.53 (d, 2H). cooled to RT filtered washed with aq. NaHSO3 dried (Na2SO4) filtered evaporated

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of i-PrMgCl (27.49 mL, 2M in THF, 55 mmol.) was added dropwise to commercially available 1,3-dibromo-2-methyl-benzene (12.5 g, 50 mmol) at RT under argon and then heated at 65° C. for 1.5 h. The mixture was added via syringe to a suspension of dry ZnCl2 (6.83 g, 50 mmol.) in dry THF (20 ml) and cooled to 0° C. under argon. The resulting suspension was stirred at RT for 30 min. Then 2-bromo-pyridine (4.78 ml, 50 mmol.) and PdCl2*dppf (2.03 g) were added and the mixture was refluxed for 2 h. The reaction mixture was then quenched by the addition of a 5% solution of citric acid (200 ml) and extracted with ethyl acetate (2×250 ml). The combined organic layers were consecutively washed with a 5% solution of citric acid (150 ml) and brine (150 ml), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude material was chromatographed on silica gel. Yield: 7.7 g, 78%. cooled to 0° C. under argon the mixture was refluxed for 2 h The reaction mixture was then quenched by the addition of a 5% solution of citric acid (200 ml) extracted with ethyl acetate (2×250 ml) The combined organic layers were consecutively washed with a 5% solution of citric acid (150 ml) and brine (150 ml) dried over Na2SO4 filtered evaporated under reduced pressure The crude material was chromatographed on silica gel

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,6-dibromotoluene (20 g, 100 mmol) in dioxane (160 ml) was stirred under argon. Then, DIPEA (30.9 ml, 160 mmol), xantphos (2.77 g, 4.8 mmol) and Pd2(dba)3 (2.4 g, 2.4 mmol) were added and the reaction was heated to 100° C. Phenyl-methanethiol (9.4 ml, 80 mmol) was slowly added and the reaction stirred for 6 h. The reaction was quenched by the addition of 150 ml of H2O. After extraction (three times) with ethyl acetate, the combined organic layers were washed with water, dried with Na2SO4, evaporated to dryness and the product was purified by silica gel chromatography. The reaction was quenched by the addition of 150 ml of H2O After extraction (three times) with ethyl acetate the combined organic layers were washed with water dried with Na2SO4 evaporated to dryness the product was purified by silica gel chromatography