3-BROMO-5-CHLOROTOLUENE

The amine 5 or 6 (30 mmol) was dissolved in a mixture of acetic acid (60 mL), water (25 mL) and concentrated HCl (7 mL) and cooled to 5 °C. A solution of sodium nitrite (48 mmol, 3.31 g) in water (12 mL) was added dropwise, with the temperature of the mixture kept below 5 °C. The mixture was stirred at 5-10 °C for further 2 h, then poured into 50percent solution of hypophosphorous acid, cooled to 0 °C and stirred at ambient temperature for 48 h. The mixture was extracted with dichloromethane (3×120 mL). The combined organic extracts were washed with brine (100 mL), dried over anhydrous Na2SO4 and evaporated. The residue was purified by flash column chromatography.To an ice-water-cooled and stirred solution of 2-amino-5-bromo-3-chlorotoluene (12 g, 54 mmol) in a mixture of 100 mL of acetic acid, 43 mL of HThe amine 5 or 6 (30 mmol) was dissolved in a mixture of acetic acid (60 mL), water (25 mL) and concentrated HCl (7 mL) and cooled to 5 C. A solution of sodium nitrite (48 mmol, 3.31 g) in water (12 mL) was added dropwise, with the temperature of the mixture kept below 5 C. The mixture was stirred at 5-10 C for further 2 h, then poured into 50% solution of hypophosphorous acid, cooled to 0 C and stirred at ambient temperature for 48 h. The mixture was extracted with dichloromethane (3×120 mL). The combined organic extracts were washed with brine (100 mL), dried over anhydrous Na2SO4 and evaporated. The residue was purified by flash column chromatography.Under a nitrogen atmosphere, a 5 L dry and clean four-neck round bottom flask was charged with diisopropylamine (72.8 g, 0.72 mol, 1.06 eq) and 1500 mL of anhydrous tetrahydrofuran, and the temperature was reduced to -70 C.Add n-butyllithium solution (272mL, 2.5M, 0.68mol, 1.0eq), and reduce the temperature to -70 with stirring.Slowly add D-2 (139g, 0.68mol, 1.0eq) and maintain the reaction for 1h after the addition.Slowly add iodine-tetrahydrofuran solution (172g iodine / 300ml THF, 0.68mol, 1.0eq), After the addition, the reaction was maintained for 1 h.The temperature was slowly raised to room temperature, and the reaction was monitored by HPLC for completion.The reaction was quenched with 500 mL of 5% Na2S2O3 solution, and extracted with 2 L of methyl tert-butyl ether. The organic phase was washed with 1500 mL of saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain an oil, and recrystallized by adding 650 mL of ethanol.182 g (F-2) of white flake solid was obtained, Yield was 81%.

Molecular Weight:205.48
XLogP3:3.6
Exact Mass:203.93414
Monoisotopic Mass:203.93414
Heavy Atom Count:9
Complexity:94.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes