3-bromo-5-tert-butylphenol

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 403 mg of 3-bromo-5-tert-butylphenol and 200 mg (1.28 mmol) of CuCN in 5 mL of DMF was stirred at 160° C. After 75 min. 365 mg of CuCN was added and stirring was continued at 160° C. After about 1 h, the temperature was increased to 170° C. and the mixture was refluxed for 19 h. Ethyl acetate and H2O were added, and the mixture was filtered through a Buchner funnel, and the layers were separated. The organic layer was washed with 10 mL of H2O and brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (15% EtOAc/hexanes) provided 153 mg of 3-tert-butyl-5-hydroxybenzonitrile as an orange solid in 49% yield. was continued at 160° C After about 1 h the mixture was refluxed for 19 h the mixture was filtered through a Buchner funnel the layers were separated The organic layer was washed with 10 mL of H2O and brine dried over Na2SO4 filtered concentrated Purification by flash silica gel chromatography (15% EtOAc/hexanes)

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

Procedure: To a stirring solution of 34 mL of 1.6 M n-BuLi in hexanes in 20 mL of THF at −78° C. was added 8.15 g of 1,3-dibromo-5-tert-butylbenzene in 80 mL of THF dropwise over a period of 1 h. After 1 h at −78° C., 4.6 mL of B(OMe)3 was added, and after 20 min. the cold bath was removed and stirring continued with warming to r.t. After 1 h, EtOAc and 70 mL of 1 N HCl were added, and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. To a stirring mixture of the crude product in 105 mL of 1 N NaOH at 0° C. was added 22 mL of H2O2 (30 wt % in H2O) dropwise. After 25 min. 5 N HCl was added to a pH=1. Ethyl acetate was added, and the organic layer was washed with 80 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (hexanes to 10% EtOAc/hexanes) provided 6.54 g of 3-bromo-5-tert-butylphenol as an orange oil with some impurity. after 20 min. the cold bath was removed After 1 h EtOAc and 70 mL of 1 N HCl were added the layers were separated The organic layer was washed with brine dried over Na2SO4 filtered concentrated To a stirring mixture of the crude product in 105 mL of 1 N NaOH at 0° C. was added 22 mL of H2O2 (30 wt % in H2O) dropwise After 25 min 5 N HCl was added to a pH=1 Ethyl acetate was added the organic layer was washed with 80 mL of brine dried over Na2SO4 filtered concentrated Purification by flash silica gel chromatography (hexanes to 10% EtOAc/hexanes)