2-(4-bromo-2-fluorophenyl)ethanol

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

Procedure: The title compound was synthesized according to the same general procedure described for the synthesis of 4-bromo-1-(2-iodo-ethyl)-2-methyl-benzene in Preparation #2, Step 1, except that 2-(4-bromo-2-fluoro-phenyl)-ethanol was used instead of 2-(4-bromo-2-methylphenyl)ethanol to yield the title compound as a clear oil (5.75 g, 95.7%) 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.13-3.24 (m, 2H) 3.26-3.44 (m, 2H) 7.06-7.14 (m, 1H) 7.21-7.24 (m, 1H) 7.26-7.31 (m, 1H) The title compound was synthesized

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-fluoro-phenyl-acetic acid (36 g, 154 mmol) (40.6 g, 174 mmol) was dissolved in THF (100 mL), and cooled to 0° C. in an ice-bath. Borane (1 M in THF, 200 mL, 1.2 eq) was then added dropwise. During the addition, the temperature rose slowly to 27° C. After complete addition the ice-bath was removed and the reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL), and the obtained suspension was diluted with H2O (500 mL). The THF layer was separated and concentrated under reduced pressure. The aqueous layer was extracted with EtOAc (2×100 mL). The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure, yielding crude material (35.6 g) as a yellow oil, which solidified to a white solid upon standing. The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2), yielding the title compound as a white solid (31.5 g, 144 mmol, 82%). 1H-NMR (CDCl3, 300 MHz): 1.50 (s, 1H); 2.95 (t, 2H); 3.92 (t, 2H); 7.18 (t, 1H); 7.28 (m, 1H) During the addition rose slowly to 27° C was removed The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL) the obtained suspension was diluted with H2O (500 mL) The THF layer was separated concentrated under reduced pressure The aqueous layer was extracted with EtOAc (2×100 mL) The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine The organic layer was dried (Na2SO4) filtered concentrated under reduced pressure yielding crude material (35.6 g) as a yellow oil, which The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-fluoro-phenyl-acetic acid (36 g, 154 mmol) (40.6 g, 174 mmol) was dissolved in THF (100 mL), and cooled to 0° C. in an ice-bath. Borane (1 M in THF, 200 mL, 1.2 eq) was then added dropwise. During the addition, the temperature rose slowly to 27° C. After complete addition the ice-bath was removed and the reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL), and the obtained suspension was diluted with H2O (500 mL). The THF layer was separated and concentrated under reduced pressure. The aqueous layer was extracted with EtOAc (2×100 mL). The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure, yielding crude material (35.6 g) as a yellow oil, which solidified to a white solid upon standing. The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2), yielding the title compound as a white solid (31.5 g, 144 mmol, 82%). 1H-NMR (CDCl3, 300 MHz): 1.50 (s, 1H); 2.95 (t, 2H); 3.92 (t, 2H); 7.18 (t, 1H); 7.28 (m, 1H) During the addition rose slowly to 27° C was removed The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL) the obtained suspension was diluted with H2O (500 mL) The THF layer was separated concentrated under reduced pressure The aqueous layer was extracted with EtOAc (2×100 mL) The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine The organic layer was dried (Na2SO4) filtered concentrated under reduced pressure yielding crude material (35.6 g) as a yellow oil, which The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2)

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

Procedure: A solution of 2-(4-bromo-2-fluorophenyl)ethanol (3.01 mmol) in dichloromethane (5 mL) and pyridine (10 mL) was treated with 4-(dimethylamino)pyridine (0.151 mmol) and acetic anhydride (9.04 mmol). The reaction was stirred overnight at room temperature. At this point the reaction was diluted with dichloromethane (100 mL). The organic layer was washed three times with 1N aq HCl, once with saturated aq sodium bicarbonate, and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a pale beige oil (710 mg, 81% yield). 1H NMR (400 MHz, DMSO-d6) d ppm 1.96 (s, 3 H) 2.90 (t, J=6.44 Hz, 2 H) 4.20 (t, J=6.57 Hz, 2 H) 7.26-7.43 (m, 2 H) 7.51 (dd, J=9.73, 1.89 Hz, 1 H). The organic layer was washed three times with 1N aq HCl The organic layer was dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: The title compound was synthesized according to the same general procedure described for the synthesis of 4-bromo-1-(2-iodo-ethyl)-2-methyl-benzene in Preparation #2, Step 1, except that 2-(4-bromo-2-fluoro-phenyl)-ethanol was used instead of 2-(4-bromo-2-methylphenyl)ethanol to yield the title compound as a clear oil (5.75 g, 95.7%) 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.13-3.24 (m, 2H) 3.26-3.44 (m, 2H) 7.06-7.14 (m, 1H) 7.21-7.24 (m, 1H) 7.26-7.31 (m, 1H) The title compound was synthesized

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-fluoro-phenyl-acetic acid (36 g, 154 mmol) (40.6 g, 174 mmol) was dissolved in THF (100 mL), and cooled to 0° C. in an ice-bath. Borane (1 M in THF, 200 mL, 1.2 eq) was then added dropwise. During the addition, the temperature rose slowly to 27° C. After complete addition the ice-bath was removed and the reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL), and the obtained suspension was diluted with H2O (500 mL). The THF layer was separated and concentrated under reduced pressure. The aqueous layer was extracted with EtOAc (2×100 mL). The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure, yielding crude material (35.6 g) as a yellow oil, which solidified to a white solid upon standing. The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2), yielding the title compound as a white solid (31.5 g, 144 mmol, 82%). 1H-NMR (CDCl3, 300 MHz): 1.50 (s, 1H); 2.95 (t, 2H); 3.92 (t, 2H); 7.18 (t, 1H); 7.28 (m, 1H) During the addition rose slowly to 27° C was removed The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL) the obtained suspension was diluted with H2O (500 mL) The THF layer was separated concentrated under reduced pressure The aqueous layer was extracted with EtOAc (2×100 mL) The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine The organic layer was dried (Na2SO4) filtered concentrated under reduced pressure yielding crude material (35.6 g) as a yellow oil, which The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2)