4-bromo-1-cyclopentyl-2-(trifluoromethyl)benzene

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

Procedure: In a 15 mL round-bottomed flask were placed 4-bromo-1-cyclopentyl-2-(trifluoromethyl)benzene (0.186 g, 0.635 mmol) and anhydrous THF (1.86 mL) under argon atmosphere. The solution was stirred well and cooled to −78° C. (dry ice IPA bath). BuLi (2.5 M in hexanes, 0.281 mL, 0.703 mmol) was added in drops (slowly) and the reaction mixture was stirred at low temperature for 25 min. Anhydrous DMF (0.1 mL, 0.766 mmol) was added in drops at −78° C. (slowly). The mixture was stirred at −78° C. for 20 min then at room temperature for 30 min. The reaction was quenched with water, acidified with 2 M HCl and extracted with EtOAc. The EtOAc layer was washed with water, dried over Na2SO4, and concentrated in vacuo to give the title compound as an oil (60 mg). LCMS m/z=243.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.7 (m, 4H), 1.79-1.94 (m, 2H), 1.95-2.09 (m, 2H), 3.29-3.37 (m, 1H), 7.86 (d, J=8 Hz, 1H), 8.12 (d, J=8 Hz, 1H), 8.16 (d, J=1.2 Hz, 1H), 10.46 (s, 1H). In a 15 mL round-bottomed flask were placed was stirred at low temperature for 25 min The mixture was stirred at −78° C. for 20 min The reaction was quenched with water extracted with EtOAc The EtOAc layer was washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, concentrated H2SO4 (2.5 mL) was added, and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography

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

Procedure: In a 15 mL round-bottomed flask were placed 4-bromo-1-cyclopentyl-2-(trifluoromethyl)benzene (0.186 g, 0.635 mmol) and anhydrous THF (1.86 mL) under argon atmosphere. The solution was stirred well and cooled to −78° C. (dry ice IPA bath). BuLi (2.5 M in hexanes, 0.281 mL, 0.703 mmol) was added in drops (slowly) and the reaction mixture was stirred at low temperature for 25 min. Anhydrous DMF (0.1 mL, 0.766 mmol) was added in drops at −78° C. (slowly). The mixture was stirred at −78° C. for 20 min then at room temperature for 30 min. The reaction was quenched with water, acidified with 2 M HCl and extracted with EtOAc. The EtOAc layer was washed with water, dried over Na2SO4, and concentrated in vacuo to give the title compound as an oil (60 mg). LCMS m/z=243.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.7 (m, 4H), 1.79-1.94 (m, 2H), 1.95-2.09 (m, 2H), 3.29-3.37 (m, 1H), 7.86 (d, J=8 Hz, 1H), 8.12 (d, J=8 Hz, 1H), 8.16 (d, J=1.2 Hz, 1H), 10.46 (s, 1H). In a 15 mL round-bottomed flask were placed was stirred at low temperature for 25 min The mixture was stirred at −78° C. for 20 min The reaction was quenched with water extracted with EtOAc The EtOAc layer was washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, concentrated H2SO4 (2.5 mL) was added, and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, concentrated H2SO4 (2.5 mL) was added, and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography

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

Procedure: In a 15 mL round-bottomed flask were placed 4-bromo-1-cyclopentyl-2-(trifluoromethyl)benzene (0.186 g, 0.635 mmol) and anhydrous THF (1.86 mL) under argon atmosphere. The solution was stirred well and cooled to −78° C. (dry ice IPA bath). BuLi (2.5 M in hexanes, 0.281 mL, 0.703 mmol) was added in drops (slowly) and the reaction mixture was stirred at low temperature for 25 min. Anhydrous DMF (0.1 mL, 0.766 mmol) was added in drops at −78° C. (slowly). The mixture was stirred at −78° C. for 20 min then at room temperature for 30 min. The reaction was quenched with water, acidified with 2 M HCl and extracted with EtOAc. The EtOAc layer was washed with water, dried over Na2SO4, and concentrated in vacuo to give the title compound as an oil (60 mg). LCMS m/z=243.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.7 (m, 4H), 1.79-1.94 (m, 2H), 1.95-2.09 (m, 2H), 3.29-3.37 (m, 1H), 7.86 (d, J=8 Hz, 1H), 8.12 (d, J=8 Hz, 1H), 8.16 (d, J=12 Hz, 1H), 10.46 (s, 1H). In a 15 mL round-bottomed flask were placed was stirred at low temperature for 25 min The mixture was stirred at −78° C. for 20 min The reaction was quenched with water extracted with EtOAc The EtOAc layer was washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, concentrated H2SO4 (2.5 mL) was added, and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography

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

Procedure: In a 15 mL round-bottomed flask were placed 4-bromo-1-cyclopentyl-2-(trifluoromethyl)benzene (0.186 g, 0.635 mmol) and anhydrous THF (1.86 mL) under argon atmosphere. The solution was stirred well and cooled to −78° C. (dry ice IPA bath). BuLi (2.5 M in hexanes, 0.281 mL, 0.703 mmol) was added in drops (slowly) and the reaction mixture was stirred at low temperature for 25 min. Anhydrous DMF (0.1 mL, 0.766 mmol) was added in drops at −78° C. (slowly). The mixture was stirred at −78° C. for 20 min then at room temperature for 30 min. The reaction was quenched with water, acidified with 2 M HCl and extracted with EtOAc. The EtOAc layer was washed with water, dried over Na2SO4, and concentrated in vacuo to give the title compound as an oil (60 mg). LCMS m/z=243.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.7 (m, 4H), 1.79-1.94 (m, 2H), 1.95-2.09 (m, 2H), 3.29-3.37 (m, 1H), 7.86 (d, J=8 Hz, 1H), 8.12 (d, J=8 Hz, 1H), 8.16 (d, J=12 Hz, 1H), 10.46 (s, 1H). In a 15 mL round-bottomed flask were placed was stirred at low temperature for 25 min The mixture was stirred at −78° C. for 20 min The reaction was quenched with water extracted with EtOAc The EtOAc layer was washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, concentrated H2SO4 (2.5 mL) was added, and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography

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

Procedure: In a 15 mL round-bottomed flask were placed 4-Bromo-1-cyclopentyl-2-(trifluoromethyl)benzene (0.186 g, 0.635 mmol) and anhydrous THF (1.86 mL) under argon atmosphere. The solution was stirred well and cooled to −78° C. (dry ice IPA bath). BuLi (2.5 M in hexanes, 0.281 mL, 0.703 mmol) was added in drops (slowly) and the reaction mixture was stirred at low temperature for 25 min. Anhydrous DMF (0.1 mL, 0.766 mmol) was added in drops at −78° C. (slowly). The mixture was stirred at −78° C. for 20 min then in room temperature for 30 min. The reaction was quenched with water, acidified with 2M HCl and extracted with EtOAc. The EtOAc layer was washed with water, dried over Na2SO4, and concentrated in vacuo to give the title compound as an oil (60 mg). LCMS m/z=243.3 [M+H]+. NMR (400 MHz, DMSO-d6) (δ ppm 1.55-1.7 (m, 4H), 1.79-1.94 (m, 2H), 1.95-2.09 (m, 2H), 3.29-3.37 (m, 1H), 7.86 (d, J=8 Hz, 1H), 8.12 (d, J=8 Hz, 1H), 8.16 (d, J=1.2 Hz, 1H), 10.46 (s, 1H). In a 15 mL round-bottomed flask were placed was stirred at low temperature for 25 min The mixture was stirred at −78° C. for 20 min The reaction was quenched with water extracted with EtOAc The EtOAc layer was washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, added concentrated H2SO4 (2.5 mL), and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography

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

Procedure: To a solution of 1-cyclopentyl-2-(trifluoromethyl)benzene (0.5 g, 2.334 mmol) in acetic acid (2.5 mL) was added bromine (1.202 mL, 23.34 mmol). The mixture was stirred well, added concentrated H2SO4 (2.5 mL), and stirred at 40° C. for 1.5 h. The reaction mixture was poured into ice-water and extracted with CH2Cl2. The CH2Cl2 layer was washed with water, followed by a solution of sodium thiosulfate, then with water. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (250 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52-1.75 (m, 4H), 1.78-1.88 (m, 2H), 1.95-2.04 (m, 2H), 3.16-3.26 (m, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.81 (dd, J=8.4 Hz, 2 Hz, 1H). stirred at 40° C. for 1.5 h extracted with CH2Cl2 The CH2Cl2 layer was washed with water The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure The residue was purified by silica gel chromatography