3-(Trifluoromethyl)benzenepropanol

Brown Oil

3-[3-(trifluoromethyl)phenyl]propan-1-ol is an organofluorine compound that is 3-phenylpropan-1-ol bearing a trifluoromethyl group at position 3 on the phenyl ring. It is an organofluorine compound and a member of propan-1-ols.

To a solution of 14.5 g (72.5 mmol) of purified 3-(3-trifluoromethylphenyl) propynol in 50 mL of 2-propanol, 0.38 g of 10percent Pd/C (Selcat Q6) was added. The reaction mixture was hydrogenated at a temperature of 42-45° C. and a pressure of 5 bars until all starting material was reacted (approximately 5 hours). The catalyst was removed by filtration and washed with a small amount of 2-propanol. The obtained solution was then evaporated in vacuo. The resulting crude product (14.5 g, 100.0percent) was purified by vacuum distillation to yield 10.5 g (Yield: 72.1percent) of pure Compound VII product as a nearly colorless oil (bp.: 58-60° C./1.1-1.5 mbar).In 1000ML autoclave, followed by adding solvent ethanol 600ML, Trifluoromethyl cinnamyl alcohol 202G, KT-02 hydrogenation catalyst 35G, After the autoclave was sealed with nitrogen, Access to hydrogen to pressure 2.0MPa and warmed to 60 ° C, the reaction 6 hours, Trifluoromethyl cinnamyl alcohol disappeared completely. The reaction solution was filtered, Concentrated to a light yellow oily liquid 202.8G, a yield of 99.4percent.Example 8A solution of methyl 3-(3'-trifluoromethylphenyl)propionate in methanol (content 20percent by weight) was passed at 40 g/h under a hydrogen pressure of 200 bar and at 160° C. through a reactor with 100 ml of the catalyst of the composition 56percent CuO, 15percent Cu, 24percent Al3-(3-Trifluoromethyl-phenyl)-propionic acid (12.4 g, 57 mmol) was dissolved in THF (160 ml) in an inert atmosphere and cooled to 0° C. followed by slow addition of borane in THF (85 ml, 85 mmol). 3-(3-Trifluoromethyl-phenyl)-propionic acid (12.4 g, 57 mmol) was dissolved in THF (160 ml) in an inert atmosphere and cooled to 0°C followed by slow addition of borane in THF (85 ml, 85 mmol). 2000mL three-necked flask, 109 g of m-trifluoromethylphenylpropionic acid (500 mmol) were added, 900 mL 2-methyltetrahydrofuran, 56 g of N-methylmorpholine (550 mmol, 1.1 eq.), Cold to -10 , 59 g of ethyl chloroformate (550 mmol, 1.1 eq.) Was added dropwise, Control temperature below -5 , About 40min plus finished, the reaction 60min, The resulting N-methylmorpholine hydrochloride was filtered off, A solution of 28.5 g of NaBH4 (750 mmol, 1.5 eq.) In 200 g of water was added dropwise to the filtrate, Add about 2h, the control temperature at 0-5 , the reaction is completed 3h.After the reaction was completed, the solvent was concentrated under reduced pressure and extracted twice with 600 mL of methylene chloride. The combined organic phases were washed twice with 300 mL of 1N NaOH, twice with 200 mL of saturated brine, The organic phase was dried over 40 g of anhydrous sodium sulfate for 4 h, After filtration, the dichloromethane was concentrated, Residual liquid 2mmHg distilled under reduced pressure to give a colorless transparent liquid 94.1 g, yield 92.2percent, purity 99.7percent.Preparation of 3-(3-trifluoromethylphenyl) propan-1-ol; Compound obtained from Example 1(0.463 moles, 100 gms) was suspended in 500 ml of tetrahydrofuran under stirring. The reaction mass was cooled to 0-53-(3-Trifluoromethyl-phenyl)-propionic acid (12.4 g, 57 mmol) was dissolved in THF (160 ml) in an inert atmosphere and cooled to 0 C. followed by slow addition of borane in THF (85 ml, 85 mmol). Stirring was continued at 0 C. for 1 h and at rt for 24 h. The mixture was cooled to 0 C. and methanol (100 ml) and water (100 ml) was carefully added. The organic solvents were removed under reduced pressure. The remaining aqueous layer was extracted with DCM (3*100 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silicagel, DCM/methanol=9/1) to give 10.97 g (94%) of 3-(3-trifluoromethyl-phenyl)-propan-1-ol. LC-MS: tR=0.87 min; [M+H]+=no ionisation.3-(3-Trifluoromethyl-phenyl)-propionic acid (12.4 g, 57 mmol) was dissolved in THF (160 ml) in an inert atmosphere and cooled to 0C followed by slow addition of borane in THF (85 ml, 85 mmol). Stirring was continued at 0C for 1 h and at rt for 24 h. The mixture was cooled to 0C and methanol (100 ml) and water (100 ml) was carefully added. The organic solvents were removed under reduced pressure. The remaining aqueous layer was extracted with DCM (3 x 100 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silicagel, DCM / methanol = 9 / 1) to give 10.97 g (94%) of 3-(3-trifluoromethyl-phenyl)-propan-1-ol. LC-MS: tR = 0.87 min; [M+H]+ = no ionisation.2000mL three-necked flask, 109 g of m-trifluoromethylphenylpropionic acid (500 mmol) were added, 900 mL 2-methyltetrahydrofuran, 56 g of N-methylmorpholine (550 mmol, 1.1 eq.), Cold to -10 , 59 g of ethyl chloroformate (550 mmol, 1.1 eq.) Was added dropwise, Control temperature below -5 , About 40min plus finished, the reaction 60min, The resulting N-methylmorpholine hydrochloride was filtered off, A solution of 28.5 g of NaBH4 (750 mmol, 1.5 eq.) In 200 g of water was added dropwise to the filtrate, Add about 2h, the control temperature at 0-5 , the reaction is completed 3h.After the reaction was completed, the solvent was concentrated under reduced pressure and extracted twice with 600 mL of methylene chloride. The combined organic phases were washed twice with 300 mL of 1N NaOH, twice with 200 mL of saturated brine, The organic phase was dried over 40 g of anhydrous sodium sulfate for 4 h, After filtration, the dichloromethane was concentrated, Residual liquid 2mmHg distilled under reduced pressure to give a colorless transparent liquid 94.1 g, yield 92.2%, purity 99.7%.Preparation of 3-(3-trifluoromethylphenyl) propan-1-ol; Compound obtained from Example 1(0.463 moles, 100 gms) was suspended in 500 ml of tetrahydrofuran under stirring. The reaction mass was cooled to 0-50C. 94% solution of borane dimethyl sulfide solution (0.62 moles, 50 ml) was added drop wise maintaining the temperature of 0-5C.The reaction mass was stirred at 25-3O0C for about 10 hours.10%HCI (100 ml) was added drop wise to the reaction mass at 25-3O0C in about 2 hours and then extracted with toluene (2x 250 ml).The organic layer was separated and washed with water (5 x 500 ml).Toluene was removed completely from the organic layer by distillation under vacuum to isolate the title compound as an oil (85 gms, Yield 90%).EXAMPLE 17: PROCESS FOR THE PREPARATION OF 3-(3- TRIFLUOROMETHYL-PHENYL)-PROPAN-1-OL.3-[3-(trifluromethyl) phenyl] propanoic acid (2.94 g) and tetrahydrofuran (30 ml) were taken into a round bottom flask followed by stirring for about 10 minutes under nitrogen atmosphere. Lithium aluminium hydride (0.5 g) was added slowly over about 5 minutes. The resultant reaction solution was stirred for about 35 EPO A solution of 3-(3-trifluoromethyl-phenyl)-propionic acid (300g, 1.375mol) in toluene (1.5 L) was azeotroped for 1 hour and cooled to 40-45 0C. Thereafter, borane-dimethylsufide (126.52g, 1.67mol) was added and reaction mixture was heated for 3-4 hours at 85C and cooled to 0-50C. The reaction mixture was quenched with methanol (900ml) and stirred at 0-50C for 1 hour. Solvent was distilled off under vacuum 50-550C. The resulting residue was dissolved in toluene (900ml) and washed with water (600ml). Toluene was distilled off under vacuum at 60-650C to give 274.38g of the title compound having purity 97% by HPLC.(12-1) Synthesis of 3-(3-trifluoromethylphenyl)-1-propanol (compound 12-1) 3-Trifluoromethylcinnamic acid (10.0 g) was dissolved in methanol (50 ml) and tetrahydrofuran (30 ml), 10% palladium carbon (5.00 g) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 11 hr. The reaction container was purged with nitrogen, the solution was filtered, and the filtrate was concentrated to give a white powder (10.4 g). The white powder was dissolved in tetrahydrofuran (100 ml), and a tetrahydrofuran-borane tetrahydrofuran solution (1 mol/l, 60.2 ml) was added dropwise to the mixture under ice-cooling, and the mixture was stirred under ice-cooling for 30 min, and further at room temperature for 16 hr. To the reaction mixture was added water, 1 mol/l aqueous hydrochloric acid solution was added, and the mixture was extracted with ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object product (9.00 g) as a pale-yellow oil. 1H-NMR(CDCl3) delta (ppm): 1.56(1H, brs), 1.87-1.95(2H, m), 2.78(2H, t, J=7.5Hz), 3.69(2H, t, J=6.4Hz), 7.38-7.48(4H, m).Preparation of 3-(3-trifluoromethyl-phenyl)-propan-1-ol Method A: To a solution of 3-(3-trifluoromethyl-phenyl)-propionic acid (5 g, 0.023 mol) in tetrahydrofuran (25 ml) was added borane-dimethylsufide (1.74 g, 0.023 mol) and refluxed for 2 hours. Reaction mixture was cooled and methanol (10 ml) was added at 5-10 C. Solvents were distilled off followed by addition of isopropylether (25 ml) and 5N hydrochloric acid (20 ml). The reaction mixture was heated at 45-50 C. for 2 hours and then cooled to 25-30 C. The layers were separated; organic layer was washed with water, dried and evaporated to give 4.11 g of the title compound. Method B: A solution of 3-(3-trifluoromethyl-phenyl)-propionic acid (300 g, 1.375 mol) in toluene (1.5 L) was azeotroped for 1 hour and cooled to 40-45 C. Thereafter, borane-dimethylsufide (126.52 g, 1.67 mol) was added and reaction mixture was heated for 3-4 hours at 85 C. and cooled to 0-5 C. The reaction mixture was quenched with methanol (900 ml) and stirred at 0-5 C. for 1 hour. Solvent was distilled off under vacuum 50-55 C. The resulting residue was dissolved in toluene (900 ml) and washed with water (600 ml). Toluene was distilled off under vacuum at 60-65 C. to give 274.38 g of the title compound having purity 97% by HPLC.General procedure: To a stirred solution of 3- or 4-substituted phenylpropanoic acid 51-63 (7.0 mmol) in dry THF (35 ml), borane dimethyl sulfide (21.0 mmol) was added dropwise at 0 oC. The reaction mixture was stirred for 18h at room temperature, quenched with H2O and concentrated in vacuo. The resulting residue was re-dissolved in diethyl ether (25 ml), and washed with 10%NaOH (30ml) and brine. The organic fraction was dried over Na2SO4, filtered, and concentrated in vacuo to give 3-phenylpropan-1-ol derivatives that were used in the next step without further purification.3-(3-Trifluoromethyl-phenyl)-propionic acid (12.4 g, 57 mmol) was dissolved in THF (160 ml) in an inert atmosphere and cooled to 0 C. followed by slow addition of borane in THF (85 ml, 85 mmol). Stirring was continued at 0 C. for 1 h and at rt for 24 h. The mixture was cooled to 0 C. and methanol (100 ml) and water (100 ml) was carefully added. The organic solvents were removed under reduced pressure. The remaining aqueous layer was extracted with DCM (3*100 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silicagel, DCM/methanol=9/1) to give 10.97 g (94%) of 3-(3-trifluoromethyl-phenyl)-propan-1-ol. LC-MS: tR=0.87 min; [M+H]+=no ionisation.3-(3-Trifluoromethyl-phenyl)-propionic acid (12.4 g, 57 mmol) was dissolved in THF (160 ml) in an inert atmosphere and cooled to 0C followed by slow addition of borane in THF (85 ml, 85 mmol). Stirring was continued at 0C for 1 h and at rt for 24 h. The mixture was cooled to 0C and methanol (100 ml) and water (100 ml) was carefully added. The organic solvents were removed under reduced pressure. The remaining aqueous layer was extracted with DCM (3 x 100 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silicagel, DCM / methanol = 9 / 1) to give 10.97 g (94%) of 3-(3-trifluoromethyl-phenyl)-propan-1-ol. LC-MS: tR = 0.87 min; [M+H]+ = no ionisation.2000mL three-necked flask, 109 g of m-trifluoromethylphenylpropionic acid (500 mmol) were added, 900 mL 2-methyltetrahydrofuran, 56 g of N-methylmorpholine (550 mmol, 1.1 eq.), Cold to -10 , 59 g of ethyl chloroformate (550 mmol, 1.1 eq.) Was added dropwise, Control temperature below -5 , About 40min plus finished, the reaction 60min, The resulting N-methylmorpholine hydrochloride was filtered off, A solution of 28.5 g of NaBH4 (750 mmol, 1.5 eq.) In 200 g of water was added dropwise to the filtrate, Add about 2h, the control temperature at 0-5 , the reaction is completed 3h.After the reaction was completed, the solvent was concentrated under reduced pressure and extracted twice with 600 mL of methylene chloride. The combined organic phases were washed twice with 300 mL of 1N NaOH, twice with 200 mL of saturated brine, The organic phase was dried over 40 g of anhydrous sodium sulfate for 4 h, After filtration, the dichloromethane was concentrated, Residual liquid 2mmHg distilled under reduced pressure to give a colorless transparent liquid 94.1 g, yield 92.2%, purity 99.7%.Preparation of 3-(3-trifluoromethylphenyl) propan-1-ol; Compound obtained from Example 1(0.463 moles, 100 gms) was suspended in 500 ml of tetrahydrofuran under stirring. The reaction mass was cooled to 0-50C. 94% solution of borane dimethyl sulfide solution (0.62 moles, 50 ml) was added drop wise maintaining the temperature of 0-5C.The reaction mass was stirred at 25-3O0C for about 10 hours.10%HCI (100 ml) was added drop wise to the reaction mass at 25-3O0C in about 2 hours and then extracted with toluene (2x 250 ml).The organic layer was separated and washed with water (5 x 500 ml).Toluene was removed completely from the organic layer by distillation under vacuum to isolate the title compound as an oil (85 gms, Yield 90%).EXAMPLE 17: PROCESS FOR THE PREPARATION OF 3-(3- TRIFLUOROMETHYL-PHENYL)-PROPAN-1-OL.3-[3-(trifluromethyl) phenyl] propanoic acid (2.94 g) and tetrahydrofuran (30 ml) were taken into a round bottom flask followed by stirring for about 10 minutes under nitrogen atmosphere. Lithium aluminium hydride (0.5 g) was added slowly over about 5 minutes. The resultant reaction solution was stirred for about 35 EPO A solution of 3-(3-trifluoromethyl-phenyl)-propionic acid (300g, 1.375mol) in toluene (1.5 L) was azeotroped for 1 hour and cooled to 40-45 0C. Thereafter, borane-dimethylsufide (126.52g, 1.67mol) was added and reaction mixture was heated for 3-4 hours at 85C and cooled to 0-50C. The reaction mixture was quenched with methanol (900ml) and stirred at 0-50C for 1 hour. Solvent was distilled off under vacuum 50-550C. The resulting residue was dissolved in toluene (900ml) and washed with water (600ml). Toluene was distilled off under vacuum at 60-650C to give 274.38g of the title compound having purity 97% by HPLC.(12-1) Synthesis of 3-(3-trifluoromethylphenyl)-1-propanol (compound 12-1) 3-Trifluoromethylcinnamic acid (10.0 g) was dissolved in methanol (50 ml) and tetrahydrofuran (30 ml), 10% palladium carbon (5.00 g) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 11 hr. The reaction container was purged with nitrogen, the solution was filtered, and the filtrate was concentrated to give a white powder (10.4 g). The white powder was dissolved in tetrahydrofuran (100 ml), and a tetrahydrofuran-borane tetrahydrofuran solution (1 mol/l, 60.2 ml) was added dropwise to the mixture under ice-cooling, and the mixture was stirred under ice-cooling for 30 min, and further at room temperature for 16 hr. To the reaction mixture was added water, 1 mol/l aqueous hydrochloric acid solution was added, and the mixture was extracted with ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object product (9.00 g) as a pale-yellow oil. 1H-NMR(CDCl3) delta (ppm): 1.56(1H, brs), 1.87-1.95(2H, m), 2.78(2H, t, J=7.5Hz), 3.69(2H, t, J=6.4Hz), 7.38-7.48(4H, m).Preparation of 3-(3-trifluoromethyl-phenyl)-propan-1-ol Method A: To a solution of 3-(3-trifluoromethyl-phenyl)-propionic acid (5 g, 0.023 mol) in tetrahydrofuran (25 ml) was added borane-dimethylsufide (1.74 g, 0.023 mol) and refluxed for 2 hours. Reaction mixture was cooled and methanol (10 ml) was added at 5-10 C. Solvents were distilled off followed by addition of isopropylether (25 ml) and 5N hydrochloric acid (20 ml). The reaction mixture was heated at 45-50 C. for 2 hours and then cooled to 25-30 C. The layers were separated; organic layer was washed with water, dried and evaporated to give 4.11 g of the title compound. Method B: A solution of 3-(3-trifluoromethyl-phenyl)-propionic acid (300 g, 1.375 mol) in toluene (1.5 L) was azeotroped for 1 hour and cooled to 40-45 C. Thereafter, borane-dimethylsufide (126.52 g, 1.67 mol) was added and reaction mixture was heated for 3-4 hours at 85 C. and cooled to 0-5 C. The reaction mixture was quenched with methanol (900 ml) and stirred at 0-5 C. for 1 hour. Solvent was distilled off under vacuum 50-55 C. The resulting residue was dissolved in toluene (900 ml) and washed with water (600 ml). Toluene was distilled off under vacuum at 60-65 C. to give 274.38 g of the title compound having purity 97% by HPLC.General procedure: To a stirred solution of 3- or 4-substituted phenylpropanoic acid 51-63 (7.0 mmol) in dry THF (35 ml), borane dimethyl sulfide (21.0 mmol) was added dropwise at 0 oC. The reaction mixture was stirred for 18h at room temperature, quenched with H2O and concentrated in vacuo. The resulting residue was re-dissolved in diethyl ether (25 ml), and washed with 10%NaOH (30ml) and brine. The organic fraction was dried over Na2SO4, filtered, and concentrated in vacuo to give 3-phenylpropan-1-ol derivatives that were used in the next step without further purification.Synthesis of 3-[3-(trifluoromethyl)phenyl]-propionaldehyde (II) A solution of compound (V) (1.0 g, 4.90 mmol) in dichloromethane (20 ml) is cooled in water / ice bath, treated in succession with DMSO (770 mg, 9.80 mmol) and P2O5 (1.39 g, 9.80 mmol) and left under stirring for 30 minutes, while temperature raises to 20C. The reaction mixture is then cooled in water / ice bath and triethylamine (2.4 ml, 17.15 mmol). The resulting solution is kept under stirring while temperature raises to 20C. After one hour the mixture is treated with 5% HCl, the phases are separated and the organic one is further washed with 5% HCl. The organic phase is then washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure, to afford 0.99 g of the aldehyde of formula (II) in quantitative yield. 1H NMR (300 MHz, CDCl3), ppm: 9.83 (t, 1H, J 0.9 Hz), 7.48-7.38 (m, 4H), 3.02 (t, 2H, J 7.2 Hz), 2.82 (m, 2H).Synthesis of 3-[3-(trifluoromethyl)phenyl]-propionaldehyde (II) A solution of compound (V) (1.0 g, 4.90 mmol) in dichloromethane (20 ml) is cooled in water/ice bath, treated in succession with DMSO (770 mg, 9.80 mmol) and P2O5 (1.39 g, 9.80 mmol) and left under stirring for 30 minutes, while temperature raises to 20 C. The reaction mixture is then cooled in water/ice bath and triethylamine (2.4 ml, 17.15 mmol). The resulting solution is kept under stirring while temperature raises to 20 C. After one hour the mixture is treated with 5% HCl, the phases are separated and the organic one is further washed with 5% HCl. The organic phase is then washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure, to afford 0.99 g of the aldehyde of formula (II) in quantitative yield. 1H NMR (300 MHz, CDCl3), ppm: 9.83 (t, 1H, J 0.9 Hz), 7.48-7.38 (m, 4H), 3.02 (t, 2H, J 7.2 Hz), 2.82 (m, 2H).(I) To a solution of 3-[3-(trifluoromethyl)phenyl]propan-l-ol (IV) (lOOg, 0.49 mol) in toluene (2 L) at -10C to -15C, dimethyl sulfide (30 g, 0.4828 mol) and triethyl amine (62g, 0.6127mol) were added in a single lot under argon and stirred for 15- 30 min. N-Chlorosuccinamide (180 g, 1.3480mol) was added lot wise over lhr while maintaining the internal temperature at -10Cto -15C. The reaction mixture was stirred for 3hr at -10C to -15C. Completion of reaction was monitored by Gas Chromatography(GC) or Thin layer chromatography (TLC). After completion of reaction, dilute Sodium hydroxide solution (40 g in 1200mL of water) was added slowly at temperature less than -5C. After the addition, the mixture was warmed to 20Candstirred for 1 hr at 20C. The aqueous and organic layers were separated and the product from organic layer was extracted with sodium bisulphate solution(140 g in l lOOmL of water). The product layer was washed with dichloromethane (200mL). Sodium carbonate solution (25% inwater) was added to product aqueous layer to adjust pH to 9.5 to 9.8. The product was extracted with dichloromethane and concentrated under vaccum to give 3-[3- (trifluoromethyl)phenyl]propionaldehydeasayellowoil(84 g, 85% yield).Step 3: Preparation of Compound III (i.e., 3-(3-trifluoromethylphenyl)propanal) To a solution of 10 g (48 mmol) of Compound VII, 76.6 mg of TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy free radical) and 234 mg of potassium bromide in 70 mL methylene chloride was added 220 mL (pH=9.5) of sodium hypochlorite solution over 20 minutes at 10-15 C. with stirring. After five minutes of additional stirring, the organic layer was separated. The aqueous layer was extracted twice with 40 mL of methylene chloride, and the collected organic layers were dried and evaporated to yield 10 g of crude Compound III as a yellowish liquid. Yield: 100%; purity (determined by GC): 90.3%, contains 8.25% of Compound NMR data (200 MHz, CDCl3, ppm): 2.81 (t, 2H), 3.00 (t, 21-1), 7.37-7.46 (m, 4H), 9.80 (s, 1H).A solution of (R) -N- [1- (1-naphthyl) ethyl] -2-nitrobenzenesulfonamide in toluene (83 g pure)92 g of triphenylphosphine, 72 g of 3- (3-trifluoromethylphenyl) propanol and 125 mL of toluene were added and stirred. Adjust the solution temperature to 50 ° C, DiisopropylazodicarboxylateA diluted solution obtained by adding 330 mL of toluene to 71 g was dropped. After the dripping end50 mL of toluene was added and stirred at 50 ° C. for 1 hour.After completion of the reaction, 133 g of anhydrous magnesium chloride and 42 mL of toluene were added. After stirring at 50 ° C. for 2 hours, the liquid temperature was cooled to 0 ° C.The reaction solution was filtered to remove insolubles, and then washed with 415 mL of toluene cooled to 0° 415 mL of tap water was added to the filtrate and stirred, and the aqueous layer was removed by liquid separation operation. The same operation was repeated twice, and the obtained organic layer was concentrated under reduced pressure at 55 ° C. to 1165 mL, (R) -N- [1- (1-naphthyl) ethyl] -3- [3- (trifluoromethyl) phenyl]Propane-2-nitrobenzenesulfonamide tolueneA solution was obtained (pure yield 127 g, pure yield 100percent, chemical purity 92percent).

Cinacalcet hydrochloride intermediate.

Molecular Weight:204.19
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:204.07619946
Monoisotopic Mass:204.07619946
Topological Polar Surface Area:20.2
Heavy Atom Count:14
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes