2-bromo-6-methylphenol

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

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

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 500 g of the so-obtained 6-bromo-2-methylphenol, together with 10 g zinc shavings, are heated to about 100° C. Within 20 minutes 453 g benzyl chloride are added dropwise with stirring and under moisture exclusion. For a further 12 minutes the reaction mixture is heated to 150° C. It is then held a total of 5 hours at the temperature of 150° C. After cooling, the zinc is separated. The reaction product is distilled in a vacuum at 0.03 up to 0.04 Torr. 305 g 6-bromo-2-methyl-4-benzylphenol are obtained as a weakly yellowish, oily liquid, which is nearly odorless. a total of 5 hours at the temperature of 150° C After cooling the zinc is separated The reaction product is distilled in a vacuum at 0.03 up to 0.04 Torr

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

Procedure: A round bottom flask was charged with (S)-2-(4-benzylpiperazin-2-yl)ethanol (1.5 g, 6.8 mmol), 2-bromo-6-methylphenol (1.4 g, 7.5 mmol), di-tert-butyl azodicarboxylate (DBAD, 2.4 g, 10.2 mmol), polymer supported-triphenylphosphine (3.8 g, 13.6 mmol) and tetrahydrofuran (30 mL). The reaction stirred for 16 hours. The resin was removed via filtration and the solution was concentrated. Purification via flash chromatography (0-30% methanol/dichloromethane) afforded the title compound. The resin was removed via filtration the solution was concentrated Purification via flash chromatography (0-30% methanol/dichloromethane)

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

Procedure: A round bottom flask was charged with (S)-2-(4-benzylpiperazin-2-yl)ethanol (1.5 g, 6.8 mmol), 2-bromo-6-methylphenol (1.4 g, 7.5 mmol), di-tert-butyl azodicarboxylate (DBAD, 2.4 g, 10.2 mmol), polymer supported-triphenylphosphine (3.8 g, 13.6 mmol) and tetrahydrofuran (30 mL). The reaction stirred for 16 hours. The resin was removed via filtration and the solution was concentrated. Purification via flash chromatography (0-30% methanol/dichloromethane) afforded the title compound. The resin was removed via filtration the solution was concentrated Purification via flash chromatography (0-30% methanol/dichloromethane)

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

Procedure: To a solution of 2-bromo-6-methylphenol (34.6 g, 0.18 mol) in THF (300 mL) was added NaH (9.6 g, 0.24 mol, 60%) in several portions. After the mixture was stirred for 1 h, Me2SO4 (28.0 g, 0.22 mol) was added dropwise. Then the mixture was stirred over night. Water (50 mL) was added, and the solvent was removed under reduced pressure. Then the residue was dissolved in Et2O (250 mL) and the organic layer was washed with NaOH (5%, 100 mL), brine (100 mL), and dried with Na2SO4. After removing the solvent, 35.3 g of the crude product was obtained (yield: 95%). 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 3.81 (s, 3H), 6.88 (t, J=8.0 Hz, 1H), 7.10 (d, J=8.0 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H). Then the mixture was stirred over night the solvent was removed under reduced pressure Then the residue was dissolved in Et2O (250 mL) the organic layer was washed with NaOH (5%, 100 mL), brine (100 mL) dried with Na2SO4 After removing the solvent

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

Procedure: To a solution of o-cresol (20.0 g, 0.19 mol) and iPr2NH (2.63 mL, 18.5 mmol) in CH2Cl2 (500 mL), a solution of NBS (32.9 g, 0.19 mol) in CH2Cl2 (500 mL) was added dropwise over 7 h and the mixture was stirred over night at room temperature. The reaction mixture was acidified to pH=1 with conc. sulfuric acid and water (400 mL). The organic layer was separated, dried with Na2SO4, and concentrated under reduced pressure. 34.6 g of the crude product was obtained (yield: 97%). 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3H), 5.54 (s, 2H), 6.71 (t, J=7.6 Hz, 1H), 7.05 (d, J=7.6 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H). The organic layer was separated dried with Na2SO4 concentrated under reduced pressure

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

Procedure: To a solution of 2-bromo-6-methylphenol (34.6 g, 0.18 mol) in THF (300 mL) was added NaH (9.6 g, 0.24 mol, 60%) in several portions. After the mixture was stirred for 1 h, Me2SO4 (28.0 g, 0.22 mol) was added dropwise. Then the mixture was stirred over night. Water (50 mL) was added, and the solvent was removed under reduced pressure. Then the residue was dissolved in Et2O (250 mL) and the organic layer was washed with NaOH (5%, 100 mL), brine (100 mL), and dried with Na2SO4. After removing the solvent, 35.3 g of the crude product was obtained (yield: 95%). 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 3.81 (s, 3H), 6.88 (t, J=8.0 Hz, 1H), 7.10 (d, J=8.0 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H). Then the mixture was stirred over night the solvent was removed under reduced pressure Then the residue was dissolved in Et2O (250 mL) the organic layer was washed with NaOH (5%, 100 mL), brine (100 mL) dried with Na2SO4 After removing the solvent

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

Procedure: To a solution of o-cresol (20.0 g, 0.19 mol) and iPr2NH (2.63 mL, 18.5 mmol) in CH2Cl2 (500 mL), a solution of NBS (32.9 g, 0.19 mol) in CH2Cl2 (500 mL) was added dropwise over 7 h and the mixture was stirred over night at room temperature. The reaction mixture was acidified to pH=1 with conc. sulfuric acid and water (400 mL). The organic layer was separated, dried with Na2SO4, and concentrated under reduced pressure. 34.6 g of the crude product was obtained (yield: 97%). 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3H), 5.54 (s, 2H), 6.71 (t, J=7.6 Hz, 1H), 7.05 (d, J=7.6 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H). The organic layer was separated dried with Na2SO4 concentrated under reduced pressure

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

Procedure: To a solution of 2-bromo-6-methylphenol (34.6 g, 0.18 mol) in THF (300 mL), NaH (9.6 g, 0.24 mol, 60%) was added in several portions. After the mixture was stirred for 1 h, Me2SO4 (28.0 g, 0.22 mol) was added dropwise, then the mixture was stirred over night. H2O (50 mL) was added, and the solvent was removed under reduced pressure. Then the residue was dissolved in Et2O (250 mL), and was washed with NaOH (5%, 100 mL), brine (100 mL), and dried with Na2SO4. After removing the solvent, 35.3 g of the crude product was obtained. (Yield: 95%). 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3 H), 3.81 (s, 3 H), 6.88 (t, J=8.0 Hz, 1H), 7.10 (d, J=8.0 Hz, 1 H), 7.30 (d, J=7.6 Hz, 1 H). the mixture was stirred over night the solvent was removed under reduced pressure Then the residue was dissolved in Et2O (250 mL) was washed with NaOH (5%, 100 mL), brine (100 mL) dried with Na2SO4 After removing the solvent

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

Procedure: To a solution of o-cresol (20.0 g, 0.19 mol) and iPr2NH (2.63 mL, 18.5 mmol) in CH2Cl2 (500 mL), a solution of NBS (32.9 g, 0.19 mol) in CH2Cl2 (500 mL) was added dropwise over 7 h and the mixture was stirred over night at room temperature. The reaction mixture was acidified to pH=1 with conc. sulfuric acid and water (400 mL). The organic layer was separated, dried with Na2SO4, and concentrated under reduced pressure. 34.6 g of the crude product was obtained (yield: 97%). 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3 H), 5.54 (s, 2 H), 6.71 (t, J=7.6 Hz, 1 H), 7.05 (d, J=7.6 Hz, 1 H), 7.28 (d, J=8.0 Hz, 1 H). The organic layer was separated dried with Na2SO4 concentrated under reduced pressure

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

Procedure: To a solution of o-cresol (20.0 g, 0.19 mol) and iPr2NH (2.63 mL, 18.5 mmol) in CH2Cl2 (500 mL), a solution of NBS (32.9 g, 0.19 mol) in CH2Cl2 (500 mL) was added dropwise over 7 h and the mixture was stirred over night at room temperature. The reaction mixture was acidified to pH=1 with conc. sulfuric acid and water (400 mL). The organic layer was separated, dried with Na2SO4, and concentrated under reduced pressure. 34.6 g of the crude product was obtained (yield: 97%). 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3 H), 5.54 (s, 2 H), 6.71 (t, J=7.6 Hz, 1 H), 7.05 (d, J=7.6 Hz, 1 H), 7.28 (d, J=8.0 Hz, 1 H). The organic layer was separated dried with Na2SO4 concentrated under reduced pressure