4-bromo-2,6-diethylbenzonitrile

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an inert atmosphere, lithium aluminum hydride (359 mg, 9.4 mmol) was suspended in anhydrous THF (9 mL) was cooled to 0° C. and then a solution of 4-bromo-2,6-diethylbenzonitrile (1.73 g, 7.36 mmol) in anhydrous THF (3 mL) was added dropwise. The reaction mixture was then allowed to warm to ambient temperature and stirring was continued for 20 h. Sodium sulfate decahydrate (6 g) was then added to quench the reaction and the resultant reaction mixture was filtered then the filtrate was then evaporated under reduced pressure. The resultant oil was purified by flash chromatography (silica, 50 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as an orange oil (96 mg, 5%). 1H NMR (DMSO-D6, 400 MHz): 7.18 (s, 2H), 3.68 (s, 2H), 2.73-2.64 (m, 4H), 2.52-2.48 (m, 2H), 1.19-1.11 (m, 6H). to warm to ambient temperature to quench the reaction the resultant reaction mixture was filtered the filtrate was then evaporated under reduced pressure The resultant oil was purified by flash chromatography (silica, 50 g column, ISCO, 0-10% methanol in DCM)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2,6-diethylaniline (4.80 g, 21.0 mmol) was suspended in a mixture of water (25 mL) and concentrated hydrochloric acid (8.0 mL) then sonicated for 10 minutes. The resultant suspension was cooled to 0° C. and a solution of sodium nitrite (1.60 g, 23.1 mmol) in water (5 mL) was slowly added, maintaining the reaction temperature below 5° C. After 30 minutes, the reaction mixture was neutralised by the careful addition of sodium bicarbonate, then the resultant suspension was added in aliquots to a solution of copper (I) cyanide (2.26 g, 25.2 mmol) and potassium cyanide (3.43 g, 52.6 mmol) in water (25 mL) at 70° C. After complete addition, heating at 70° C. was continued for 1 h then the reaction mixture was cooled to ambient temperature. Water and DCM were added then the organic phase was collected, dried over anhydrous sodium sulfate and concentrated in vacuo to afford a brown residue that was purified by flash chromatography (silica, 80 g column, ISCO, 0-10% ethyl acetate in cyclohexane) to afford the title compound as an off-white solid (4.43 g, 88%). 1H NMR (DMSO-D6, 300 MHz): 7.58 (s, 2H), 2.78 (q, J=7.6 Hz, 4H), 1.21 (t, J=7.6 Hz, 6H). then sonicated for 10 minutes maintaining the reaction temperature below 5° C After complete addition was continued for 1 h the reaction mixture was cooled to ambient temperature the organic phase was collected dried over anhydrous sodium sulfate concentrated in vacuo to afford a brown residue that was purified by flash chromatography (silica, 80 g column, ISCO, 0-10% ethyl acetate in cyclohexane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an inert atmosphere, lithium aluminum hydride (359 mg, 9.4 mmol) was suspended in anhydrous THF (9 mL) was cooled to 0° C. and then a solution of 4-bromo-2,6-diethylbenzonitrile (1.73 g, 7.36 mmol) in anhydrous THF (3 mL) was added dropwise. The reaction mixture was then allowed to warm to ambient temperature and stirring was continued for 20 h. Sodium sulfate decahydrate (6 g) was then added to quench the reaction and the resultant reaction mixture was filtered then the filtrate was then evaporated under reduced pressure. The resultant oil was purified by flash chromatography (silica, 50 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as an orange oil (96 mg, 5%). 1H NMR (DMSO-D6, 400 MHz): 7.18 (s, 2H), 3.68 (s, 2H), 2.73-2.64 (m, 4H), 2.52-2.48 (m, 2H), 1.19-1.11 (m, 6H). to warm to ambient temperature to quench the reaction the resultant reaction mixture was filtered the filtrate was then evaporated under reduced pressure The resultant oil was purified by flash chromatography (silica, 50 g column, ISCO, 0-10% methanol in DCM)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2,6-diethylaniline (4.80 g, 21.0 mmol) was suspended in a mixture of water (25 mL) and concentrated hydrochloric acid (8.0 mL) then sonicated for 10 minutes. The resultant suspension was cooled to 0° C. and a solution of sodium nitrite (1.60 g, 23.1 mmol) in water (5 mL) was slowly added, maintaining the reaction temperature below 5° C. After 30 minutes, the reaction mixture was neutralised by the careful addition of sodium bicarbonate, then the resultant suspension was added in aliquots to a solution of copper (I) cyanide (2.26 g, 25.2 mmol) and potassium cyanide (3.43 g, 52.6 mmol) in water (25 mL) at 70° C. After complete addition, heating at 70° C. was continued for 1 h then the reaction mixture was cooled to ambient temperature. Water and DCM were added then the organic phase was collected, dried over anhydrous sodium sulfate and concentrated in vacuo to afford a brown residue that was purified by flash chromatography (silica, 80 g column, ISCO, 0-10% ethyl acetate in cyclohexane) to afford the title compound as an off-white solid (4.43 g, 88%). 1H NMR (DMSO-D6, 300 MHz): 7.58 (s, 2H), 2.78 (q, J=7.6 Hz, 4H), 1.21 (t, J=7.6 Hz, 6H). then sonicated for 10 minutes maintaining the reaction temperature below 5° C After complete addition was continued for 1 h the reaction mixture was cooled to ambient temperature the organic phase was collected dried over anhydrous sodium sulfate concentrated in vacuo to afford a brown residue that was purified by flash chromatography (silica, 80 g column, ISCO, 0-10% ethyl acetate in cyclohexane)