1-cyclopentyl-2-(trifluoromethyl)benzene

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer, thermocouple, and nitrogen inlet, was added dry THF (35 L) and cooled to 0-5° C. To the flask was added Iron (III) chloride (2.7 kg, 0.15 eq) portion wise over 30-60 min. and stirred for 15-30 min. resulting in a clear greenish solution. Under a nitrogen atmosphere in a dry 100 gallon glass lined reactor was added THF (87.5 L) and magnesium turnings (4.05 kg, 1.5 eq), and cooled to 0-5° C. To the THF and magnesium mixture was added the solution of FeCl3 in THF at a rate to maintain the internal temperature below 10° C. To the resulting yellow/green mixture was added TMEDA (15.5 kg, 1.2 eq) at a rate to maintain the internal temperature below 20° C. The resulting reaction mixture was heated to 40-45° C. for 1 hour and a mixture of 1 bromo-2-(trifluoromethyl)benzene (25 kg, 1.0 eq) and bromocyclopentane (19.9 kg, 1.2 eq) was added to the reaction mixture at a rate to maintain an internal temperature below 25° C. The resulting reaction mixture was allowed to stir at room temperature overnight and subsequently cooled to an internal temperature of 0-5° C. To the resulting mixture was added 6 N HCl (100 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic). After the quench, MTBE (200 L) was added and the reactor contents was stirred for 30 min. The phases were separated and the aqueous layer back extracted with MTBE (75 L). The combined organic layers were washed with H2O (50 L), brine (50 L) and dried (MgSO4). The mixture was filtered through an in-line (1 micron) filter cartridge followed by an additional in-line (0.45 micron) filter cartridge into a clean dry reactor. The solvent was evaporated under vacuum (jacket≦30° C.) and co-evaporated with heptanes (2×25 L) to provide a viscous liquid. The viscous liquid was dissolved in heptanes (100 L) and passed through a silica plug (25 kg). The silica plug was eluted with heptanes (TLC, Rf˜0:8, silica gel, heptanes) and the fractions containing the product were evaporated to provide the title compound as a yellow liquid, 11.7 kg (49.2%), purity as determined by HPLC was 94.1%. 1H NMR conforms to reference standard. To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer resulting in a clear greenish solution cooled to 0-5° C to maintain the internal temperature below 10° C to maintain the internal temperature below 20° C The resulting reaction mixture was heated to 40-45° C. for 1 hour was added to the reaction mixture at a rate to maintain an internal temperature below 25° C The resulting reaction mixture to stir at room temperature overnight subsequently cooled to an internal temperature of 0-5° C to maintain the internal temperature below 15° C. (caution, very exothermic) the reactor contents was stirred for 30 min The phases were separated the aqueous layer back extracted with MTBE (75 L) The combined organic layers were washed with H2O (50 L), brine (50 L) dried (MgSO4) The mixture was filtered through an in-line (1 micron) filter cartridge filter cartridge into a clean dry reactor The solvent was evaporated under vacuum (jacket≦30° C.) to provide a viscous liquid The silica plug was eluted with heptanes (TLC, Rf˜0:8, silica gel, heptanes) the fractions containing the product were evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(2-(trifluoromethyl)phenyl)cyclopentanol (5.1 g, 22.15 mmol) in ethanol (32 mL) was added 10% Pd—C (500 mg; Degussa; wet) and the mixture was hydrogenated overnight with a hydrogen balloon. The reaction mixture was filtered through Celite®. The filtrate was poured into ice-water (100 mL) and extracted with CH2Cl2 (2×70 mL). The combined CH2Cl2 layer was washed with water (1×75 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure to give the title compound (4.3 g). 1H NMR (400 MHz, CDCl3) δ ppm 1.58-1.67 (m, 4H), 1.81-1.90 (m, 2H), 2.06-2.15 (m, 2H), 3.32-3.43 (m, 1H), 7.22-7.26 (m, 1H), 7.45-7.51 (m, 2H), 7.58 (d, J=8 Hz, 1H). The reaction mixture was filtered through Celite® The filtrate was poured into ice-water (100 mL) extracted with CH2Cl2 (2×70 mL) The combined CH2Cl2 layer was washed with water (1×75 mL) dried over Na2SO4 filtered the solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(2-(trifluoromethyl)phenyl)cyclopentanol (5.1 g, 22.15 mmol) in ethanol (32 mL) was added 10% Pd—C (500 mg; Degussa; wet) and the mixture was hydrogenated overnight with a hydrogen balloon. The reaction mixture was filtered through Celite®. The filtrate was poured into ice-water (100 mL) and extracted with CH2Cl2 (2×70 mL). The combined CH2Cl2 layer was washed with water (1×75 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure to give the title compound (4.3 g). 1H NMR (400 MHz, CDCl3) δ ppm 1.58-1.67 (m, 4H), 1.81-1.90 (m, 2H), 2.06-2.15 (m, 2H), 3.32-3.43 (m, 1H), 7.22-7.26 (m, 1H), 7.45-7.51 (m, 2H), 7.58 (d, J=8 Hz, 1H). The reaction mixture was filtered through Celite® The filtrate was poured into ice-water (100 mL) extracted with CH2Cl2 (2×70 mL) The combined CH2Cl2 layer was washed with water (1×75 mL) dried over Na2SO4 filtered the solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 30 L jacketed reactor, dry THF (6 L) and magnesium turnings (243.0 g, 10 mol, 1.5 eq.) were added under N2. In a separate flask, FeCl3 (162 g, 1.0 mol, 0.15 eq.) was dissolved in THF (800 mL) (caution, exothermic) under N2. This dark brown solution was cooled to ambient temperature using an ice bath and then added over 35 min to the 30 L reactor contents under N2 at an internal temperature of 10° C. To this yellow/green mixture, TMEDA (1.2 L) was added keeping the internal temperature below 20° C. (slightly exothermic). The resulting rust brown mixture was stirred at 45° C. for 1 h under N2. The reactor content was allowed to cool below 20° C. and a mixture of 1-bromo-2-(trifluoromethyl)benzene (1500 g, 6.67 mol) and bromocyclopentane (1192 g, 8.00 mol, 1.2 eq.) added dropwise under N2 at such a rate as to maintain the internal temperature between 25-30° C. (caution, exothermic). After the addition (3.33 h) and the exotherm subsided, the reaction mixture was stirred at 25° C. under N2 overnight, allowed to cool to an internal temperature of 0° C. and quenched with 6 NHCL (3 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic). After the quench, ethyl acetate (4 L) was added and the reactor content stirred at ambient temperature for 1 h. The phases were separated and the aqueous layer back extracted with ethyl acetate (2.5 L). The combined organic layers were washed with H2O (1 L), brine (1.5 L) and dried (Na2SO4). The solvent was rotary evaporated at 35° C. and the residue fraction distilled under high vacuum (65-70° C., 0.15 Torr) to give 823 g of product (58%, not wt % corrected) as a clear colorless liquid. 1H NMR (Bruker, 400 MHz, DMSO-d6) δ ppm 7.58-7.64 (m, 3H, ArH), 7.34-7.4 (m, 1H, ArH), 3.21-3.29 (m, 1H, —CH), 1.95-2.04 (m, 2H, —CH2), 1.76-1.88 (m, 2H, —CH2), 1.49-1.71 (m, 4H, —CH2). added over 35 min to the 30 L reactor contents under N2 at an internal temperature of 10° C the internal temperature below 20° C. to cool below 20° C. added dropwise under N2 at such a rate as to maintain the internal temperature between 25-30° C. (caution, exothermic) After the addition (3.33 h) to cool to an internal temperature of 0° C. quenched with 6 NHCL (3 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic) After the quench, ethyl acetate (4 L) was added the reactor content stirred at ambient temperature for 1 h The phases were separated the aqueous layer back extracted with ethyl acetate (2.5 L) The combined organic layers were washed with H2O (1 L), brine (1.5 L) dried (Na2SO4) The solvent was rotary evaporated at 35° C. the residue fraction distilled under high vacuum (65-70° C., 0.15 Torr)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 30 L jacketed reactor, dry THF (6 L) and magnesium turnings (243.0 g, 10 mol, 1.5 eq.) were added under N2. In a separate flask, FeCl3 (162 g, 1.0 mol, 0.15 eq.) was dissolved in THF (800 mL) (caution, exothermic) under N2. This dark brown solution was cooled to ambient temperature using an ice bath and then added over 35 min to the 30 L reactor contents under N2 at an internal temperature of 10° C. To this yellow/green mixture, TMEDA (1.2 L) was added keeping the internal temperature below 20° C. (slightly exothermic). The resulting rust brown mixture was stirred at 45° C. for 1 h under N2. The reactor content was allowed to cool below 20° C. and a mixture of 1-bromo-2-(trifluoromethyl)benzene (1500 g, 6.67 mol) and bromocyclopentane (1192 g, 8.00 mol, 1.2 eq.) added dropwise under N2 at such a rate as to maintain the internal temperature between 25-30° C. (caution, exothermic). After the addition (3.33 h) and the exotherm subsided, the reaction mixture was stirred at 25° C. under N2 overnight, allowed to cool to an internal temperature of 0° C. and quenched with 6 NHCL (3 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic). After the quench, ethyl acetate (4 L) was added and the reactor content stirred at ambient temperature for 1 h. The phases were separated and the aqueous layer back extracted with ethyl acetate (2.5 L). The combined organic layers were washed with H2O (1 L), brine (1.5 L) and dried (Na2SO4). The solvent was rotary evaporated at 35° C. and the residue fraction distilled under high vacuum (65-70° C., 0.15 Torr) to give 823 g of product (58%, not wt % corrected) as a clear colorless liquid. 1H NMR (Bruker, 400 MHz, DMSO-d6) δ ppm 7.58-7.64 (m, 3H, ArH), 7.34-7.4 (m, 1H, ArH), 3.21-3.29 (m, 1H, —CH), 1.95-2.04 (m, 2H, —CH2), 1.76-1.88 (m, 2H, —CH2), 1.49-1.71 (m, 4H, —CH2). added over 35 min to the 30 L reactor contents under N2 at an internal temperature of 10° C the internal temperature below 20° C. to cool below 20° C. added dropwise under N2 at such a rate as to maintain the internal temperature between 25-30° C. (caution, exothermic) After the addition (3.33 h) to cool to an internal temperature of 0° C. quenched with 6 NHCL (3 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic) After the quench, ethyl acetate (4 L) was added the reactor content stirred at ambient temperature for 1 h The phases were separated the aqueous layer back extracted with ethyl acetate (2.5 L) The combined organic layers were washed with H2O (1 L), brine (1.5 L) dried (Na2SO4) The solvent was rotary evaporated at 35° C. the residue fraction distilled under high vacuum (65-70° C., 0.15 Torr)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 10 L jacketed reactor was added dry THF (2.4 L) and magnesium turnings (81.0 g, 3.33 mol, 1.5 eq.) under N2. In a separate flask FeCl3 (36 g, 0.22 mol, 0.1 eq.) was dissolved in THF (150 mL) (caution, exothermic) under N2. This dark brown solution was allowed to cool to ambient temperature and then added over 10 min to the reactor content under N2 at an internal temperature of about 10° C. TMEDA (402 mL) was added to this yellow/green mixture keeping the internal temperature below about 20° C. (slightly exothermic). The resulting rust brown mixture was stirred at ambient temperature for 1 h under N2 then 1 h at 45° C. The reactor contents were allowed to cool below about 20° C. and a mixture of 1-bromo-2-(trifluoromethyl)benzene (500 g, 2.22 mol) and bromocyclopentane (397 g, 2.66 mol, 1.2 eq.) added dropwise under N2 at a rate as to maintain the internal temperature between about 25-30° C. After the addition, the reaction mixture was stirred at about 25° C. under N2 overnight, allowed to cool to an internal temperature of about 0° C. and quenched with 6 N HCl (2 L) at a rate as to maintain the internal temperature below about 15° C. (caution, exothermic). [Note: IPC's after completing the addition and stirring overnight were similar indicating that the reaction may have been completed much sooner.] After the quench, hexane (3 L) was added and the reactor contents were stirred at ambient temperature for 1 h. The phases were separated and the aqueous layer back extracted with hexane (1 L). The combined organic layers were dried (Na2SO4), slurried with silica (750 g) and filtered washing the solids with hexane (1 L). The filtrate was concentrated under reduced pressure (100 torr at 37° C.) to give an amber oil (317 g, 97.3 Area % by HPLC, 87.7 wt % by HPLC (contained residual hexane by NMR), corrected yield 58%) which was used in the next step without further purification. added over 10 min to the reactor content under N2 at an internal temperature of about 10° C the internal temperature below about 20° C. 1 h at 45° C to cool below about 20° C. added dropwise under N2 at a rate as to maintain the internal temperature between about 25-30° C After the addition to cool to an internal temperature of about 0° C. quenched with 6 N HCl (2 L) at a rate as to maintain the internal temperature below about 15° C. (caution, exothermic) the addition stirring overnight were similar indicating that the reaction the reactor contents were stirred at ambient temperature for 1 h The phases were separated the aqueous layer back extracted with hexane (1 L) The combined organic layers were dried (Na2SO4) filtered washing the solids with hexane (1 L) The filtrate was concentrated under reduced pressure (100 torr at 37° C.) to give an amber oil (317 g, 97.3 Area % by HPLC, 87.7 wt % by HPLC (contained residual hexane by NMR), corrected yield 58%) which was used in the next step without further purification

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer, thermocouple, and nitrogen inlet, was added dry THF (35 L) and cooled to 0-5° C. To the flask was added Iron (III) chloride (2.7 kg, 0.15 eq) portion wise over 30-60 min. and stirred for 15-30 min. resulting in a clear greenish solution. Under a nitrogen atmosphere in a dry 100 gallon glass lined reactor was added THF (87.5 L) and magnesium turnings (4.05 kg, 1.5 eq), and cooled to 0-5° C. To the THF and magnesium mixture was added the solution of FeCl3 in THF at a rate to maintain the internal temperature below 10° C. To the resulting yellow/green mixture was added TMEDA (15.5 kg, 1.2 eq) at a rate to maintain the internal temperature below 20° C. The resulting reaction mixture was heated to 40-45° C. for 1 hour and a mixture of 1 bromo-2-(trifluoromethyl)benzene (25 kg, 1.0 eq) and bromocyclopentane (19.9 kg, 1.2 eq) was added to the reaction mixture at a rate to maintain an internal temperature below 25° C. The resulting reaction mixture was allowed to stir at room temperature overnight and subsequently cooled to an internal temperature of 0-5° C. To the resulting mixture was added 6 N HCl (100 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic). After the quench, MTBE (200 L) was added and the reactor contents was stirred for 30 min. The phases were separated and the aqueous layer back extracted with MTBE (75 L). The combined organic layers were washed with H2O (50 L), brine (50 L) and dried (MgSO4). The mixture was filtered through an in-line (1 micron) filter cartridge followed by an additional in-line (0.45 micron) filter cartridge into a clean dry reactor. The solvent was evaporated under vacuum (jacket≦30° C.) and co-evaporated with heptanes (2×25 L) to provide a viscous liquid. The viscous liquid was dissolved in heptanes (100 L) and passed through a silica plug (25 kg). The silica plug was eluted with heptanes (TLC, Rf˜0.8, silica gel, heptanes) and the fractions containing the product were evaporated to provide the title compound as a yellow liquid, 11.7 kg (49.2%), purity as determined by HPLC was 94.1%. 1H NMR conforms to reference standard. To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer resulting in a clear greenish solution cooled to 0-5° C to maintain the internal temperature below 10° C to maintain the internal temperature below 20° C The resulting reaction mixture was heated to 40-45° C. for 1 hour was added to the reaction mixture at a rate to maintain an internal temperature below 25° C The resulting reaction mixture to stir at room temperature overnight subsequently cooled to an internal temperature of 0-5° C to maintain the internal temperature below 15° C. (caution, very exothermic) the reactor contents was stirred for 30 min The phases were separated the aqueous layer back extracted with MTBE (75 L) The combined organic layers were washed with H2O (50 L), brine (50 L) dried (MgSO4) The mixture was filtered through an in-line (1 micron) filter cartridge filter cartridge into a clean dry reactor The solvent was evaporated under vacuum (jacket≦30° C.) to provide a viscous liquid The silica plug was eluted with heptanes (TLC, Rf˜0.8, silica gel, heptanes) the fractions containing the product were evaporated

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer, thermocouple, and nitrogen inlet, was added dry THF (35 L) and cooled to 0-5° C. To the flask was added Iron (III) chloride (2.7 kg, 0.15 eq) portion wise over 30-60 min. and stirred for 15-30 min. resulting in a clear greenish solution. Under a nitrogen atmosphere in a dry 100 gallon glass lined reactor was added THF (87.5 L) and magnesium turnings (4.05 kg, 1.5 eq), and cooled to 0-5° C. To the THF and magnesium mixture was added the solution of FeCl3 in THF at a rate to maintain the internal temperature below 10° C. To the resulting yellow/green mixture was added TMEDA (15.5 kg, 1.2 eq) at a rate to maintain the internal temperature below 20° C. The resulting reaction mixture was heated to 40-45° C. for 1 hour and a mixture of 1 bromo-2-(trifluoromethyl)benzene (25 kg, 1.0 eq) and bromocyclopentane (19.9 kg, 1.2 eq) was added to the reaction mixture at a rate to maintain an internal temperature below 25° C. The resulting reaction mixture was allowed to stir at room temperature overnight and subsequently cooled to an internal temperature of 0-5° C. To the resulting mixture was added 6 N HCl (100 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic). After the quench, MTBE (200 L) was added and the reactor contents was stirred for 30 min. The phases were separated and the aqueous layer back extracted with MTBE (75 L). The combined organic layers were washed with H2O (50 L), brine (50 L) and dried (MgSO4). The mixture was filtered through an in-line (1 micron) filter cartridge followed by an additional in-line (0.45 micron) filter cartridge into a clean dry reactor. The solvent was evaporated under vacuum (jacket≦30° C.) and co-evaporated with heptanes (2×25 L) to provide a viscous liquid. The viscous liquid was dissolved in heptanes (100 L) and passed through a silica plug (25 kg). The silica plug was eluted with heptanes (TLC, Rf˜0.8, silica gel, heptanes) and the fractions containing the product were evaporated to provide the title compound as a yellow liquid, 11.7 kg (49.2%), purity as determined by HPLC was 94.1%. 1H NMR conforms to reference standard. To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer resulting in a clear greenish solution cooled to 0-5° C to maintain the internal temperature below 10° C to maintain the internal temperature below 20° C The resulting reaction mixture was heated to 40-45° C. for 1 hour was added to the reaction mixture at a rate to maintain an internal temperature below 25° C The resulting reaction mixture to stir at room temperature overnight subsequently cooled to an internal temperature of 0-5° C to maintain the internal temperature below 15° C. (caution, very exothermic) the reactor contents was stirred for 30 min The phases were separated the aqueous layer back extracted with MTBE (75 L) The combined organic layers were washed with H2O (50 L), brine (50 L) dried (MgSO4) The mixture was filtered through an in-line (1 micron) filter cartridge filter cartridge into a clean dry reactor The solvent was evaporated under vacuum (jacket≦30° C.) to provide a viscous liquid The silica plug was eluted with heptanes (TLC, Rf˜0.8, silica gel, heptanes) the fractions containing the product were evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(2-(trifluoromethyl)phenyl)cyclopentanol (5.1 g, 22.15 mmol) in ethanol (32 mL) was added 10% Pd—C (500 mg; Degussa; wet) and the mixture was hydrogenated overnight with a hydrogen balloon. The reaction mixture was filtered through Celite®. The filtrate was poured into ice-water (100 mL) and extracted with CH2Cl2 (2×70 mL). The combined CH2Cl2 layer was washed with water (1×75 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure to give the title compound (4.3 g). 1H NMR (400 MHz, CDCl3) δ ppm 1.58-1.67 (m, 4H), 1.81-1.90 (m, 2H), 2.06-2.15 (m, 2H), 3.32-3.43 (m, 1H), 7.22-7.26 (m, 1H), 7.45-7.51 (m, 2H), 7.58 (d, J=8 Hz, 1H). The reaction mixture was filtered through Celite® The filtrate was poured into ice-water (100 mL) extracted with CH2Cl2 (2×70 mL) The combined CH2Cl2 layer was washed with water (1×75 mL) dried over Na2SO4 filtered the solvent was removed under reduced pressure