2-(3-hydroxyphenyl)-2-methylpropanenitrile

Conditions: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the title product of Example 106 Step 1 (520 mg, 2.97 mmoles) and pyridinium hydrochloride (2 g, 17.3 mmol) was stirred in an oil bath at 200-220 ° C. under a drying tube and so maintained for 3 h. After cooling, the mixture was partitioned between DCM and water, further extracted, and the combined organic extracts dried over Na2SO4, filtered, and evaporated to give the title compound, 416 mg, as a brownish oil. so maintained for 3 h After cooling the mixture was partitioned between DCM and water further extracted the combined organic extracts dried over Na2SO4 filtered evaporated

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

Procedure: A solution of 2,6-Dimethylbenzyl alcohol (2.76 g, 20.3 mmol) and diisopropyl azodicarboxylate (DIAD, 4.7 g, 23.2 mmol) in THF (20 ml) was added drop wise to a solution of 2-(3-hydroxyphenyl)-2-methylpropanenitrile (Step B, 3.2 g, 19.8 mmol) and triphenylphosphine (5.28 g, 20.1 mmol) in THF (50 ml) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 16 hours, diluted with ether and washed with water. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 9:1) to give the title compound. washed with water The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 9:1)

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

Procedure: To a stirred solution of 2-(3-methoxyphenyl)-2-methylpropanenitrile (Step A, 4.5 g, 25.7 mmol) in methylene chloride (30 ml) was added BBr3 (1M in CH2Cl2, 50 ml) at −78° C. under argon, the cold bath was substituted by ice bath after 30 minutes and the reaction was stirred at the same temperature for 2 hours and then 30 minutes at room temperature. The reaction mixture was quenched by addition of ice and worked up by washing with water and brine. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (methylene chloride:ethyl acetate, 5:1) to give the title compound. 30 minutes at room temperature The reaction mixture was quenched by addition of ice by washing with water and brine The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (methylene chloride:ethyl acetate, 5:1)

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

Procedure: To a stirred solution of 2-(3-methoxyphenyl)-2-methylpropanenitrile (Step A, 4.5 g, 25.7 mmol) in methylene chloride (30 ml) was added BBr3 (1M in CH2Cl2, 50 ml) at −78° C. under argon, the cold bath was substituted by ice bath after 30 minutes and the reaction was stirred at the same temperature for 2 hours and then 30 minutes at room temperature. The reaction mixture was quenched by addition of ice and worked up by washing with water and brine. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (methylene chloride:ethyl acetate, 5:1) to give the title compound. 30 minutes at room temperature The reaction mixture was quenched by addition of ice by washing with water and brine The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (methylene chloride:ethyl acetate, 5:1)

Conditions: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the title product of Example 106 Step 1 (520 mg, 2.97 mmoles) and pyridinium hydrochloride (2 g, 17.3 mmol) was stirred in an oil bath at 200-220 ° C. under a drying tube and so maintained for 3 h. After cooling, the mixture was partitioned between DCM and water, further extracted, and the combined organic extracts dried over Na2SO4, filtered, and evaporated to give the title compound, 416 mg, as a brownish oil. so maintained for 3 h After cooling the mixture was partitioned between DCM and water further extracted the combined organic extracts dried over Na2SO4 filtered evaporated

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

Procedure: A solution of 2,6-Dimethylbenzyl alcohol (2.76 g, 20.3 mmol) and diisopropyl azodicarboxylate (DIAD, 4.7 g, 23.2 mmol) in THF (20 ml) was added drop wise to a solution of 2-(3-hydroxyphenyl)-2-methylpropanenitrile (Step B, 3.2 g, 19.8 mmol) and triphenylphosphine (5.28 g, 20.1 mmol) in THF (50 ml) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 16 hours, diluted with ether and washed with water. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 9:1) to give the title compound. washed with water The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 9:1)

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

Procedure: To a stirred solution of 2-(3-methoxyphenyl)-2-methylpropanenitrile (Step A, 4.5 g, 25.7 mmol) in methylene chloride (30 ml) was added BBr3 (1M in CH2Cl2, 50 ml) at −78° C. under argon, the cold bath was substituted by ice bath after 30 minutes and the reaction was stirred at the same temperature for 2 hours and then 30 minutes at room temperature. The reaction mixture was quenched by addition of ice and worked up by washing with water and brine. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (methylene chloride:ethyl acetate, 5:1) to give the title compound. 30 minutes at room temperature The reaction mixture was quenched by addition of ice by washing with water and brine The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (methylene chloride:ethyl acetate, 5:1)