3-(3-Trifluoromethylphenyl)propanoic acid

White Crysstalline

Preparation of 3-(3-trifluoromethylphenyl) propanoic acid; 3-trifluoromethyl cinnamic acid (0.463 moles, 100 gms) was dissolved in 1.0 It. of methanol and charged to a hydrogenating vessel. 5percent Pd/C (3 gms) was added. The reaction mass was hydrogenated at H2 pressure of 1 kg/cm2 at a temperature of 25Preparation of 3-[3-(trifluoromethyl) phenyl]-2-propanoic acid (IX). 3-[3-(trifluoromethyl) phenyl]-2-propenoic acid (50 gm, 0.231 moles), methanol (250 ml) and 10 percent palladium on carbon (2.5 gm, 5percent) was autoclaved for 2.5-3.0 h under hydrogen pressure of 4 kg at 20-25 In an inert atmosphere, Pd-C (10percent, 2.84 g) was suspended in methanol (130 ml) followed by the addition of a solution of 3-(3-trifluoromethyl-phenyl)-acrylic acid (14.21 g, 65.7 mmol). In an inert atmosphere, Pd-C (10percent, 2.84 g)was suspended in methanol (130 ml) followed by the addition of a solution of 3-(3-trifluoromethyl-phenyl)-acrylic acid (14.21 g, 65.7 mmol). To a 2L four-necked flask was added 216.0 g of m-trifluoromethylcinnamic acid (1.0 mol).1 L of water and 53.0 g of sodium carbonate (0.5 mol) were dissolved by stirring, transferred to a hydrogenation tank, and then 10 g of an additional amount was added to the hydrogenation tank.3wtpercent palladium-carbon catalyst, after nitrogen replacement, hydrogen gasThe reaction was incubated at 25±5°C and pressure of 0.2-0.3 MPa for 3 h.After the reaction was completed, the mixture was filtered, and the filtrate was adjusted to pH 3-4 with 2N dilute hydrochloric acid to precipitate a white solid, which was then added to 1L.Toluene extraction once, liquid separation, the organic layer was washed once with 1 L of water, and the layers were separated and the organic layers were combined.Concentrate under reduced pressure at a temperature of 55±5°C to obtain a colorless transparent oil.Finally, it was naturally cooled to room temperature (20±5° C.) to obtain 216.7 g of trifluoromethyl phenylpropionic acid between white solids in a yield of 99.4percent.In a flame-dried, nitrogen purged 250 mL round-bottom flask equipped with a magnetic stir bar at room temperature were placed 3-(trifluoromethyl)cinnamic acid (5.00 g, 23.13 mmol), a2:1 mixture of ethyl acetate (20 mL:10 mL), and palladium on carbon (0.150 g, 1.41 mmol). To the reaction vessel ahydrogen filled balloon was added and the resulting solution was allowed tostir for 48 hours. The mixture was then filtered through celite to yield a gray oil. The solvents were removed in vacuo. The crude product was dissolved in chloroform and re-filtered to yield 4.803 g (95percent) of the title compound as a colorless oil. This material was immediately converted to the corresponding acyl succinimide.PREPARATION OF 3-[3-(TRIFLUROMETHYL) PHENYL] PROPANOIC ACIDA solution of 3-[3-(trifluoromethyl) phenyl]-2-propenoic acid (10Og) dissolved in methanol (600 ml) was taken into an autoclave vessel, and palladium-carbon (10percent w/w) (25 g) was added to it. 4 kg/cm1) Weigh 300g of trifluoromethyl cinnamic acid in the raw material and add it to 3L of methanol.Stir and dissolve10g of Pd mass content is10percent Pd/C catalyst, Mix well to form material I, Feeding material I to the preheat module 1 of the microchannel reactor for preheating, After preheating, enter the reaction module group of the microchannel reactor. 2) The reaction module group that transports hydrogen to the microchannel reactor and the step 1) the preheated material I reacts in the reaction module group.among them:Adjust the flow rate of the slurry pump so that the flow rate of the material I is 30.0 g/min.Adjust the flow rate of the H2 gas flow meter to 420ml/min, The molar ratio of trifluoromethyl cinnamic acid to hydrogen in the raw material is 1:1.2, and the reaction temperature is 80 ° C.The temperature of the cooling module is 30 ° C, the residence time of the reaction is 28 s, and the reaction pressure is 1.0 MPa.Collecting the reaction liquid flowing out from the outlet of the cooling module for post-treatment, The post-treatment means that the catalyst is recovered by filtration, and the solvent is recovered by distillation under reduced pressure.The residue was added to 1.2 L of water and the pH of the system was adjusted to 9.0 with a 20percent NaOH solution.Then, 600 ml of ethyl acetate was added to extract, and the organic phase was discarded.The aqueous phase was adjusted to pH 2.0 to 3.0 with concentrated hydrochloric acid, and extracted with 300 ml of ethyl acetate.The liquid was separated, the aqueous phase was discarded, and the residue was dissolved in 1.5 L of n-hexane.Stir at -10 to 0 ° C for 2 hours, filter, and wash the filter cake with a small amount of n-hexane.After drying at 50 ° C for 8 hours under vacuum259.25 g of 3-(3-trifluoromethylphenyl)propanoic acid, the yield was 85.62percent, and the purity was 99.21percent.Example 14:Preparation of m-trifluoromethylhydrocinnamic acid; A stirred mixture of m-trifluoromethylhydrocinnamonitrile (243.45g) and hydrochloric acid (1.2 litres) was refluxed for 4.5 hours, cooled to 25-303-(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 (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 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 (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 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.To a 2L four-necked flask was added 216.0 g of m-trifluoromethylcinnamic acid (1.0 mol).1 L of water and 53.0 g of sodium carbonate (0.5 mol) were dissolved by stirring, transferred to a hydrogenation tank, and then 10 g of an additional amount was added to the hydrogenation tank.3wtpercent palladium-carbon catalyst, after nitrogen replacement, hydrogen gasThe reaction was incubated at 25±5°C and pressure of 0.2-0.3 MPa for 3 h.After the reaction was completed, the mixture was filtered, and the filtrate was adjusted to pH 3-4 with 2N dilute hydrochloric acid to precipitate a white solid, which was then added to 1L.Toluene extraction once, liquid separation, the organic layer was washed once with 1 L of water, and the layers were separated and the organic layers were combined.Concentrate under reduced pressure at a temperature of 55±5°C to obtain a colorless transparent oil.Finally, it was naturally cooled to room temperature (20±5° C.) to obtain 216.7 g of trifluoromethyl phenylpropionic acid between white solids in a yield of 99.4percent.In a flame-dried, nitrogen purged 250 mL round-bottom flask equipped with a magnetic stir bar at room temperature were placed 3-(trifluoromethyl)cinnamic acid (5.00 g, 23.13 mmol), a2:1 mixture of ethyl acetate (20 mL:10 mL), and palladium on carbon (0.150 g, 1.41 mmol). To the reaction vessel ahydrogen filled balloon was added and the resulting solution was allowed tostir for 48 hours. The mixture was then filtered through celite to yield a gray oil. The solvents were removed in vacuo. The crude product was dissolved in chloroform and re-filtered to yield 4.803 g (95percent) of the title compound as a colorless oil. This material was immediately converted to the corresponding acyl succinimide.PREPARATION OF 3-[3-(TRIFLUROMETHYL) PHENYL] PROPANOIC ACIDA solution of 3-[3-(trifluoromethyl) phenyl]-2-propenoic acid (10Og) dissolved in methanol (600 ml) was taken into an autoclave vessel, and palladium-carbon (10percent w/w) (25 g) was added to it. 4 kg/cm2 of anhydrous hydrogen gas pressure was passed into the reaction suspension under agitation at about 25-35 0C for about 3 hours. After the completion of the reaction, the reaction suspension was filtered on a celite bed and the celite bed was washed with methanol (100 ml). The filtrate was distilled completely at about 50 °C under a vacuum of about 650 mm/Hg to afford 95.5 g (percentyield: 94.6) of the title compound.Mass (m/z) : 218.16 a.m. u.1) Weigh 300g of trifluoromethyl cinnamic acid in the raw material and add it to 3L of methanol.Stir and dissolve10g of Pd mass content is10percent Pd/C catalyst, Mix well to form material I, Feeding material I to the preheat module 1 of the microchannel reactor for preheating, After preheating, enter the reaction module group of the microchannel reactor. 2) The reaction module group that transports hydrogen to the microchannel reactor and the step 1) the preheated material I reacts in the reaction module group.among them:Adjust the flow rate of the slurry pump so that the flow rate of the material I is 30.0 g/min.Adjust the flow rate of the H2 gas flow meter to 420ml/min, The molar ratio of trifluoromethyl cinnamic acid to hydrogen in the raw material is 1:1.2, and the reaction temperature is 80 ° C.The temperature of the cooling module is 30 ° C, the residence time of the reaction is 28 s, and the reaction pressure is 1.0 MPa.Collecting the reaction liquid flowing out from the outlet of the cooling module for post-treatment, The post-treatment means that the catalyst is recovered by filtration, and the solvent is recovered by distillation under reduced pressure.The residue was added to 1.2 L of water and the pH of the system was adjusted to 9.0 with a 20percent NaOH solution.Then, 600 ml of ethyl acetate was added to extract, and the organic phase was discarded.The aqueous phase was adjusted to pH 2.0 to 3.0 with concentrated hydrochloric acid, and extracted with 300 ml of ethyl acetate.The liquid was separated, the aqueous phase was discarded, and the residue was dissolved in 1.5 L of n-hexane.Stir at -10 to 0 ° C for 2 hours, filter, and wash the filter cake with a small amount of n-hexane.After drying at 50 ° C for 8 hours under vacuum259.25 g of An ethanolic solution of 3-Trifluoromethyl cinnamic acid (I) is dissolved in absolute Ethanol (5 volumes per gram of 3-Trifluoromethyl cinnamic acid) and hydrogenated (1 atm of H2) in the presence of palladium on carbon (10percent w/w of starting material) for 16 hours at room temperature. Then the catalyst is filtered out and the solvent is evaporated until dryness to obtain saturated carboxylic acid (II).PREPARATION OF N-[(1 R)-1-(1 -NAPTHYL) ETHYL]-3-(3- TRIFLUROMETHYL) PHENYL] PROPANAMIDE OF FORMULA V STARTING FROM 3-[3-(TRIFLUROMETHYL) PHENYL] PROPENOIC ACID3-[3-(trifluromethyl) phenyl] propenoic acid (50 g) and toluene (500 ml were taken into an autoclave vessel and 5percent Pd/C (5 g) was added to it. The reaction EPO Step (i) Preparation of 3-(3-Trifluoromethyl-phenyl)-propionic acid [Compound -I]:; Methanolic solution of 3- (Trifluoromethyl) cinnamic acid (30.0g in 270.0 mL of methanol) was hydrogenated (5.0kg/cm2 of H2) in the presence of 3.0gm palladium on carbon (10percent w/w of 3- (trifluoromethyl)cinnamic acid) for 3 hours at room temperature. Then the catalyst was filtered out and the solvent was evaporated to dryness to give 28.4 g of titled compound-I.Analytical Data 1H NMR (DMSO-d6, 400 MHz) of 3- (Trifluoromethyl) cinnamic acid: delta 6.714-6.754 (doublet, 2H); delta 7.638-7.721 (broad multiplet, 2H); delta 7.758-7.777 (doublet, 1H); delta 8.030-8.050 (doublet, 1H); delta 8.095 (singlet, 1H); delta 12.607 (singlet, 1H). 1H NMR (CDCl3, 400 MHz) of compound-I: delta 2.696-2.735 (triplet, 2H); delta 3.003-3.041 (triplet, 2H); delta 7.405-7.422 (broad multiplet, 3H); delta 7.475-7.492 (singlet, 2H).; 10.0gm of 3- (Trifluoromethyl) cinnamic acid and ethanol is charged. To this reaction mixture a slurry of 1.0gm palladium on carbon in 5.0 ml of ethanol is added. The reaction mixture is stirred at room temperature for 3 hours in a hydrogenator under hydrogen at a pressure of 5.0kg/cm2. The catalyst is filtered and the solvent is evaporated to dryness to get title compound-I.Example 8: Preparation of m-trifluoromethylhydrocinnamic acidA suspension of m-trifluoromethylcinnamic acid (194g) isopropyl alcohol (970ml) and Pd/C (19.4g, 10percent) was hydrogenated for 4 hours at 1.0 kg/cm2 hydrogen pressure. After completion (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), 10percent 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).

Pharmaceutical intermediates.

Molecular Weight:218.17
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:218.05546401
Monoisotopic Mass:218.05546401
Topological Polar Surface Area:37.3
Heavy Atom Count:15
Complexity:225
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes