2-(3-hydroxy-4-methylphenyl)acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred solution of 2-(3-Hydroxy-4-methylphenyl)acetonitrile (Step A, 2.18 g, 14.8 mmol), K2CO3 (2.66 g, 19.2 mmol) in dry DMF (20 ml) was added 2,6-Dimethylbenzyl chloride (2.97 g, 19.2 mmol) at room temperature under argon. The reaction mixture was stirred for 16 hours, diluted with EtOAc (40 ml), washed with water (20 ml) and brine. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex: ethyl acetate 2:1) to give the title compound as a white solid. washed with water (20 ml) and brine The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex: ethyl acetate 2:1)

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

Procedure: To a stirred solution of 2-(3-methoxy-4-methylphenyl)acetonitrile (5 g, 31 mmol) in dry CH2Cl2 (20 ml) was added drop wise BBr3 (1M in CH2Cl2, 10.02 g, 40 mmol) at −78° C. under argon. The reaction mixture was stirred at the same temperature for 2 hours and then at 0° C. for 5 hours or until all the starting material is consumed, quenched with ice, extracted with EtOAc (30 ml×3), the combined organic layer was washed carefully with sat NaHCO3, brine and dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex: ethyl acetate 4:1→CH2Cl2: hex 1:1) to give the title compound as an off white solid. at 0° C. for 5 hours until all the starting material is consumed quenched with ice extracted with EtOAc (30 ml×3) the combined organic layer was washed carefully with sat NaHCO3, brine dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex: ethyl acetate 4:1→CH2Cl2: hex 1:1)

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

Procedure: To a stirred solution of 2-(3-Hydroxy-4-methylphenyl)acetonitrile (Step A, 2.18 g, 14.8 mmol), K2CO3 (2.66 g, 19.2 mmol) in dry DMF (20 ml) was added 2,6-Dimethylbenzyl chloride (2.97 g, 19.2 mmol) at room temperature under argon. The reaction mixture was stirred for 16 hours, diluted with EtOAc (40 ml), washed with water (20 ml) and brine. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex: ethyl acetate 2:1) to give the title compound as a white solid. washed with water (20 ml) and brine The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex: ethyl acetate 2:1)

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

Procedure: To a stirred solution of 2-(3-Hydroxy-4-methylphenyl)acetonitrile (Step A, 2.18 g, 14.8 mmol), K2CO3 (2.66 g, 19.2 mmol) in dry DMF (20 ml) was added 2,6-Dimethylbenzyl chloride (2.97 g, 19.2 mmol) at room temperature under argon. The reaction mixture was stirred for 16 hours, diluted with EtOAc (40 ml), washed with water (20 ml) and brine. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex: ethyl acetate 2:1) to give the title compound as a white solid. washed with water (20 ml) and brine The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex: ethyl acetate 2:1)

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

Procedure: To a stirred solution of 2-(3-methoxy-4-methylphenyl)acetonitrile (5 g, 31 mmol) in dry CH2Cl2 (20 ml) was added drop wise BBr3 (1M in CH2Cl2, 10.02 g, 40 mmol) at −78° C. under argon. The reaction mixture was stirred at the same temperature for 2 hours and then at 0° C. for 5 hours or until all the starting material is consumed, quenched with ice, extracted with EtOAc (30 ml×3), the combined organic layer was washed carefully with sat NaHCO3, brine and dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex: ethyl acetate 4:1→CH2Cl2: hex 1:1) to give the title compound as an off white solid. at 0° C. for 5 hours until all the starting material is consumed quenched with ice extracted with EtOAc (30 ml×3) the combined organic layer was washed carefully with sat NaHCO3, brine dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex: ethyl acetate 4:1→CH2Cl2: hex 1:1)

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

Procedure: To a stirred solution of 2-(3-methoxy-4-methylphenyl)acetonitrile (5 g, 31 mmol) in dry CH2Cl2 (20 ml) was added drop wise BBr3 (1M in CH2Cl2, 10.02 g, 40 mmol) at −78° C. under argon. The reaction mixture was stirred at the same temperature for 2 hours and then at 0° C. for 5 hours or until all the starting material is consumed, quenched with ice, extracted with EtOAc (30 ml×3), the combined organic layer was washed carefully with sat NaHCO3, brine and dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex: ethyl acetate 4:1→CH2Cl2: hex 1:1) to give the title compound as an off white solid. at 0° C. for 5 hours until all the starting material is consumed quenched with ice extracted with EtOAc (30 ml×3) the combined organic layer was washed carefully with sat NaHCO3, brine dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex: ethyl acetate 4:1→CH2Cl2: hex 1:1)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of (3-hydroxy-4-methylphenyl)-acetonitrile (1.7 g, 11.5 mmol) in acetone (100 ml), K2CO3 (7.9 g, 57.5 mmol) and 1-bromo butane (6.1 ml, 57.5 mmol) were added. The suspension was refluxed for 24 h and the solvent was evaporated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with water and brine. The organic layer was dried over Na2SO4, filtered and the solvent evaporated under reduced pressure. The crude was purified by flash chromatography (petroleum ether:EtOAc 9.5:0.5) affording the title compound (1.43 g, 61% yield) as colourless oil. The suspension was refluxed for 24 h the solvent was evaporated under reduced pressure The residue was dissolved in CH2Cl2 washed with water and brine The organic layer was dried over Na2SO4 filtered the solvent evaporated under reduced pressure The crude was purified by flash chromatography (petroleum ether:EtOAc 9.5:0.5)

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

Procedure: To a solution of 3-methoxy-4-methylphenylacetonitrile (2.0 g, 12.4 mmol) in dry CH2Cl2 (50 ml) cooled to −78° C., BBr3 1 M in CH2Cl2 (27 ml, 27 mmol) was added dropwise. The mixture was stirred overnight allowing the cooling bath to expire. The mixture was slowly poured in ice/water under stirring. When the ice melted, the aqueous phase was extracted with EtOAc and the organic phase was dried over Na2SO4, filtered and the solvent was evaporated under reduced pressure. The crude title compound (1.7 g, 93% yield) was used in the next step without further purification. under stirring the aqueous phase was extracted with EtOAc the organic phase was dried over Na2SO4 filtered the solvent was evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-(3-methoxy-4-methylphenyl)acetonitrile (5 g, 31 mmol) in dry CH2Cl2 (20 ml) was added drop wise BBr3 (1M in CH2Cl2, 10.02 g, 40 mmol) at −78° C. under argon. The reaction mixture was stirred at the same temperature for 2 hours and then at 0° C. for 5 hours or until all the starting material is consumed, quenched with ice, extracted with EtOAc (30 ml×3), the combined organic layer was washed carefully with sat NaHCO3, brine and dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate 4:1→CH2Cl2:hex 1:1) to give the title compound as an off white solid. at 0° C. for 5 hours until all the starting material is consumed quenched with ice extracted with EtOAc (30 ml×3) the combined organic layer was washed carefully with sat NaHCO3, brine dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate 4:1→CH2Cl2:hex 1:1)

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

Procedure: To a solution of (3-hydroxy-4-methylphenyl)-acetonitrile (1.7 g, 11.5 mmol) in acetone (100 ml), K2CO3 (7.9 g, 57.5 mmol) and 1-bromo butane (6.1 ml, 57.5 mmol) were added. The suspension was refluxed for 24 h and the solvent was evaporated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with water and brine. The organic layer was dried over Na2SO4, filtered and the solvent evaporated under reduced pressure. The crude was purified by flash chromatography (petroleum ether: EtOAc 9.5:0.5) affording the title compound (1.43 g, 61% yield) as colourless oil. The suspension was refluxed for 24 h the solvent was evaporated under reduced pressure The residue was dissolved in CH2Cl2 washed with water and brine The organic layer was dried over Na2SO4 filtered the solvent evaporated under reduced pressure The crude was purified by flash chromatography (petroleum ether: EtOAc 9.5:0.5)