4-bromo-2-chloro-6-ethylphenol

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

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

Procedure: A solution of 4-Bromo-2-chloro-6-ethyl-phenol dissolved in THF (10 mL) was added to a cooled 0° C. suspension of NaH (0.43 g, 10.8 mmol, 60% dispersion in mineral oil) in THF (20 ml). After the addition was complete the reaction mixture was warmed up to room temperature and stirred for 30 mins. 2-Methoxyethoxymethyl chloride (1.34 mL, 11.7 mmol) was added and the reaction was stirred for 15 hours. The reaction mixture was quenched with 1N HCl and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to a yellow oil. Purification by flash column chromatography (0% to 10% EtOAc in hexanes) gave the title compound as a clear oil (2.4 g, 76%). 1H NMR (400 MHz, CDCl3): δ 1.21 (t, J=7.3 Hz, 3 H), 2.70 (q, J=7.6 Hz, 2 H), 3.40 (s, 3 H), 3.61 (m, 2 H), 3.98 (m, 2 H), 5.15 (s, 2 H), 7.24 (s, 1 H), 7.37 (s, 1 H). was added to a cooled 0° C. After the addition the reaction was stirred for 15 hours The reaction mixture was quenched with 1N HCl extracted with EtOAc The organic layers were washed with brine dried over Na2SO4 concentrated to a yellow oil Purification by flash column chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: A solution of 4-Bromo-2-chloro-6-ethyl-phenol dissolved in THF (10 mL) was added to a cooled 0° C. suspension of NaH (0.43 g, 10.8 mmol, 60% dispersion in mineral oil) in THF (20 ml). After the addition was complete the reaction mixture was warmed up to room temperature and stirred for 30 mins. 2-Methoxyethoxymethyl chloride (1.34 mL, 11.7 mmol) was added and the reaction was stirred for 15 hours. The reaction mixture was quenched with 1N HCl and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to a yellow oil. Purification by flash column chromatography (0% to 10% EtOAc in hexanes) gave the title compound as a clear oil (2.4 g, 76%). 1H NMR (400 MHz, CDCl3): δ 1.21 (t, J=7.3 Hz, 3 H), 2.70 (q, J=7.6 Hz, 2 H), 3.40 (s, 3 H), 3.61 (m, 2 H), 3.98 (m, 2 H), 5.15 (s, 2 H), 7.24 (s, 1 H), 7.37 (s, 1 H). was added to a cooled 0° C. After the addition the reaction was stirred for 15 hours The reaction mixture was quenched with 1N HCl extracted with EtOAc The organic layers were washed with brine dried over Na2SO4 concentrated to a yellow oil Purification by flash column chromatography (0% to 10% EtOAc in hexanes)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (1.2 g, 30 mmol) and hydrazine monohydrate (1.75 mL, 36 mmol) were added to a solution of 5′-bromo-3′-chloro-2′-hydroxyacetophenone (3 g, 12 mmol) dissolved in triethylene glycol (15 mL). The reaction mixture was heated to 160° C. for 72 hours and then partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes) to give the title compound (2.34 g, 83%). 1H NMR (400 MHz, CDCl3): δ 1.22 (t, J=7.6 Hz, 3 H), 2.65 (q, J=7.6 Hz, 2 H), 5.55 (s, 1 H), 7.17 (s, 1 H), 7.31 (s, 1 H). partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: Potassium carbonate (3.9 g, 28 mmol) followed by methyl iodide (0.58 mL, 9.3 mmol) were added to a solution of 4-bromo-2-chloro-6-ethyl-phenol (2.2 g, 9.3 mmol) in DMF (10 mL). The mixture was stirred for 20 hours and then partitioned between 1N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The crude yellow oil was purified by flash column chromatography (0% to 3% EtOAc in hexanes) to give the desired product (21 g, 91%) 1H NMR (400 MHz, CDCl3): δ 1.22 (t, J=7.6 Hz, 3 H), 2.66 (q, J=7.6 Hz, 2 H), 3.82 (s, 3 H), 7.22 (s, 1 H), 7.37 (s, 1 H). partitioned between 1N HCl and EtOAc The organic layers were washed with saturated NaHCO3, brine dried over Na2SO4 concentrated The crude yellow oil was purified by flash column chromatography (0% to 3% EtOAc in hexanes)

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

Procedure: Potassium carbonate (3.9 g, 28 mmol) followed by methyl iodide (0.58 mL, 9.3 mmol) were added to a solution of 4-bromo-2-chloro-6-ethyl-phenol (2.2 g, 9.3 mmol) in DMF (10 mL). The mixture was stirred for 20 hours and then partitioned between 1N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The crude yellow oil was purified by flash column chromatography (0% to 3% EtOAc in hexanes) to give the desired product (21 g, 91%) 1H NMR (400 MHz, CDCl3): δ 1.22 (t, J=7.6 Hz, 3 H), 2.66 (q, J=7.6 Hz, 2 H), 3.82 (s, 3 H), 7.22 (s, 1 H), 7.37 (s, 1 H). partitioned between 1N HCl and EtOAc The organic layers were washed with saturated NaHCO3, brine dried over Na2SO4 concentrated The crude yellow oil was purified by flash column chromatography (0% to 3% EtOAc in hexanes)

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

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

Procedure: A solution of 4-Bromo-2-chloro-6-ethyl-phenol dissolved in THF (10 mL) was added to a cooled 0° C. suspension of NaH (0.43 g, 10.8 mmol, 60% dispersion in mineral oil) in THF (20 ml). After the addition was complete the reaction mixture was warmed up to room temperature and stirred for 30 mins. 2-Methoxyethoxymethyl chloride (1.34 mL, 11.7 mmol) was added and the reaction was stirred for 15 hours. The reaction mixture was quenched with 1N HCl and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to a yellow oil. Purification by flash column chromatography (0% to 10% EtOAc in hexanes) gave the title compound as a clear oil (2.4 g, 76%). 1H NMR (400 MHz, CDCl3): δ 1.21 (t, J=7.3 Hz, 3H), 2.70 (q, J=7.6 Hz, 2H), 3.40 (s, 3H), 3.61 (m, 2H), 3.98 (m, 2H), 5.15 (s, 2H), 7.24 (s, 1H), 7.37 (s, 1H). was added to a cooled 0° C. After the addition the reaction was stirred for 15 hours The reaction mixture was quenched with 1N HCl extracted with EtOAc The organic layers were washed with brine dried over Na2SO4 concentrated to a yellow oil Purification by flash column chromatography (0% to 10% EtOAc in hexanes)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (1.2 g, 30 mmol) and hydrazine monohydrate (1.75 mL, 36 mmol) were added to a solution of 5′-bromo-3′-chloro-2′-hydroxyacetophenone (3 g, 12 mmol) dissolved in triethylene glycol (15 mL). The reaction mixture was heated to 160° C. for 72 hours and then partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes) to give the title compound (2.34 g, 83%). 1H NMR (400 MHz, CDCl3): δ 1.22 (t, J=7.6 Hz, 3H), 2.65 (q, J=7.6 Hz, 2H), 5.55 (s, 1H), 7.17 (s, 1H), 7.31 (s, 1H). partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: Potassium carbonate (3.9 g, 28 mmol) followed by methyl iodide (0.58 mL, 9.3 mmol) were added to a solution of 4-bromo-2-chloro-6-ethyl-phenol (2.2 g, 9.3 mmol) in DMF (10 mL). The mixture was stirred for 20 hours and then partitioned between 1N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The crude yellow oil was purified by flash column chromatography (0% to 3% EtOAc in hexanes) to give the desired product (2.1 g, 91%) 1H NMR (400 MHz, CDCl3): δ 1.22 (t, J=7.6 Hz, 3H), 2.66 (q, J=7.6 Hz, 2H), 3.82 (s, 3H), 7.22 (s, 1H), 7.37 (s, 1H). partitioned between 1N HCl and EtOAc The organic layers were washed with saturated NaHCO3, brine dried over Na2SO4 concentrated The crude yellow oil was purified by flash column chromatography (0% to 3% EtOAc in hexanes)

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

Procedure: A solution of 4-Bromo-2-chloro-6-ethyl-phenol dissolved in THF (10 mL) was added to a cooled 0° C. suspension of NaH (0.43 g, 10.8 mmol, 60% dispersion in mineral oil) in THF (20 ml). After the addition was complete the reaction mixture was warmed up to room temperature and stirred for 30 mins. 2-Methoxyethoxymethyl chloride (1.34 mL, 11.7 mmol) was added and the reaction was stirred for 15 hours. The reaction mixture was quenched with 1N HCl and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to a yellow oil. Purification by flash column chromatography (0% to 10% EtOAc in hexanes) gave the title compound as a clear oil (2.4 g, 76%). 1H NMR (400 MHz, CDCl3): δ 1.21 (t, J=7.3 Hz, 3 H), 2.70 (q, J=7.6 Hz, 2 H), 3.40 (s, 3 H), 3.61 (m, 2 H), 3.98 (m, 2 H), 5.15 (s, 2 H), 7.24 (s, 1 H), 7.37 (s, 1 H). was added to a cooled 0° C. After the addition the reaction was stirred for 15 hours The reaction mixture was quenched with 1N HCl extracted with EtOAc The organic layers were washed with brine dried over Na2SO4 concentrated to a yellow oil Purification by flash column chromatography (0% to 10% EtOAc in hexanes)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (1.2 g, 30 mmol) and hydrazine monohydrate (1.75 mL, 36 mmol) were added to a solution of 5′-bromo-3′-chloro-2′-hydroxyacetophenone (3 g, 12 mmol) dissolved in triethylene glycol (15 mL). The reaction mixture was heated to 160° C. for 72 hours and then partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes) to give the title compound (2.34 g, 83%). 1H NMR (400 MHz, CDCl3): δ 1.22 (t, J=7.6 Hz, 3 H), 2.65 (q, J=7.6 Hz, 2 H), 5.55 (s, 1 H), 7.17 (s, 1 H), 7.31 (s, 1 H). partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes)