(R)-2-((4-Nitrophenethyl)amino)-1-phenylethanol hydrochloride

To a stirred solution of (100 g) (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (prepared according to example la) in tetrahydrofuran (400 mL), sodium borohydride (44.07 g) was added at 28°C (±2). After addition of sodium borohydride, the reaction temperature was lowered to 2°C (±2). To this chilled mass, solution of iodine (169.03 g) in tetrahydrofuran (600 mL) was added slowly. Thereafter temperature was increased to reflux and mixture was stirred for 10 hrs. The reaction mixture was cooled to 5°C (±2), to which then methanol (50 mL) was added and stirred for 30 minutes. Conc. hydrochloric acid aqueous solution (35percent, 20.83 mL) was added slowly while maintaining exotherm below 10°C and the mixture was stirred for 30 minutes. The reaction mixture was allowed to warm to the 28°C (±2), water was added follOwed by heating the reaction mass at 68°C (±2) for 1 hr. Tetrahydrofuran and methanol were distilled under vacuo. The reaction mixture was cooled to 30°C (±2) and it was diluted with dichloromethane (800 mL) and aqueous ammonia solution (200 mL). To the organic layer, solution of hydrochloric acid in isopropanol (17percent, 100 mL) was added slowly and stirred it for 3 hrs. The solid obtained was filtered, washed with dichloromethane (100 mL) and dried under vacuo at 48°C (±2) to obtain (R)-2-[2’-(4-nitrophenyl)ethyl]amino]-1-phenylethanol monohydrochioride.Yield: 94.8 g (90.5percent); Purity by HPLC: 99.09percent.The intermediate (M-01) (9 g, 30 mmol, 1 eq)And NaBH4 (3.45 g, 90 mmol, 3 eq) were dissolved in dry THF (60 mL)Et2O · BF3 (11.7 mL, 90 mmol, 3 eq, w = 46.5percent) was slowly added dropwise under ice-Dripping finished insulation reaction for 20 minutes, returned to room temperature, reflux 3-4h, TLC tracking or liquid phase control reaction is completed, returned to room temperature, The solvent was concentrated in vacuo 70percent solvent, THF was recovered, Ice bath slowly dropping 1mol / L dilute hydrochloric acid (30mL) quenching reaction, And then concentrated NaOH solution to the system to alkaline (pH ≈ 9), Extracted with ethyl acetate 2-3 times, The organic phase was washed with saturated NaHCO3, dried and concentrated to an oil.The oil was dissolved in isopropanol at 50 ° C, Slowly dropwise 12 mol / L concentrated hydrochloric acid (3 mL, 1.2 eq) to precipitate a white solid, Low temperature crystallization 1h, filtration, washing with isopropyl alcohol products, The hydrochloride salt of the intermediate (M-02) was dried, Purity 99.83percent (HPLC) in 90percent yield.Compound III (20g, 0.0666mol) in 60ml1, 3--dimethyl-2-imidazolidinone and tetrahydrofuran, was added dropwise 133.2ml1mol / L borane-tetrahydrofuran solution together, 70 refluxed 4h.TLC monitoring (GFExample-2: Preparation of (R)-2-[[2'-(4-nitrophenyl)-ethyl]amino]-l-phenyIethanol mono hydrochloride (or) (R)-2-(4-nitrophenethylamino)-l-phenylethanol mono hydrochloride (Formula-5a) Borane-dimethyl sulfide (500 ml) was added to a solution of (R)-2-hydroxy-N-[2-(4-nitro phenyl)ethyl]-2-phenylacetamide compound of formula-4 (100 gms) in tetrahydrofuran (300 ml) at -10°C to -5°C and stirred for 45 mins at the same temperature. Slowly heated the reaction mixture to 70-75°C and stirred for 5 hrs at the same temperature. Cooled the reaction mixture to 0-5°C and quenched the reaction mixture by adding methanol (38.6 ml) and hydrochloric acid (78.5 ml) and stirred for 15 mins at the same temperature. Slowly heated the reaction mixture to 65-70°C and stirred for 90 mins at the same temperature. Distilled off the 50percent of the solvent from the reaction mixture under reduced pressure. 30percent aqueous potassium carbonate solution (800 ml), water (80 ml) and ethyl acetate (1000 ml) were added to the reaction mixture. Both the organic and aqueous layers were separated and distilled off the solvent completely from the organic layer under reduced pressure. Isopropanol (1000 ml) was added to the obtained compound and heated the reaction mixture to 35-40°C. Hydrochloric acid (32.7 gms) was added to the reaction mixture at 25-30°C and stirred for 15 hrs at the same temperature. Filtered the precipitated solid, washed with isopropanol and dried to get the title compound. Yield: 97.0 gms.To a stirred solution of 2-(4-Nitro-phenyl)-ethylamine hydrochloride (NPA HCI) (100.0 g) in water (600 mL); triethylamine (55.0 g) and catalytic amount of tetra-butyl ammonium bromide (TBAB) was added at 28°C (±2). To this solution, R-styrene oxide (77.05 g) was added and temperature of the solution was raised to 42°C (±2) and maintained it at this temperature for 3 hrs. The reaction mass was cooled to 28°C (±2) and diluted with dichloromethane (600 mL). The organic layer was separated and concentrated under vacuo. To the obtained residue, tetrahydrofuran (200 mL) was added and the solution cooled to 10°C. To this cooled mixture, solution of hydrochloric acid in isopropanol (17percent, 100 mL) was added. The precipitated solid was stirred, filtered, washed it with tetrahydrofuran and dried it under vacuo at 40°C to obtain (R)-2-[2 ‘-(4-nitrophenyl)ethyl]amino]- I -phenylethanol monohydrochloride.Yield: 38.3 g (24.05percent); Purity by HPLC: 96.5 percent.100.0 gm (0.342 mol) of (R)-(-)-1-phenyl-1, 2-ethanediol 2-tosylate of formula (12)and 170.6 gm (1.026 mol) of 4-nitrophenylethylamine of formula (13) and 300m1 of tetrahydrofuran (THF) were charged in a clean and dry round bottom flask and stined. The resultant reaction mixture was heated to about 60°C and stirred for about 18 hours. The reaction progress was monitored by TLC, after completion of reaction, reaction mass was cooled to about 30°C. The solid precipitated was filtered and the solid was washed with200m1 of tetrahydrofuran (THF). The filtrates were combined and distilled off under reduced pressure to afford the syrup. The resultant syrup was suspended in 300m1 of methyl tertiary butyl ether (MTBE) and treated with 13percent w/w (144.2 gm (0.5 13 mol) of IPA/HC1 (HC1 gas suspended in isopropyl alcohol) for about 1 hour at about 25-35°C. The separated solid was filtered and the solid was washed with MTBE followed by slurry wash with water. The solidobtained was dried till to get constant weight to yield 70 gms of (R)-1-Phenyl-2-[[2-(4- nitrophenyl)ethyl] aminojethanol hydrochloride of formula (2) as crystalline solid.M.P: 194.1-197.4°C; SOR: [11125: -35° (c=0.5 in MeOH);FTIR (KBr): 3542, 2990, 2442, 1607, 1598, 1522, 1441, 1347, 1315, 1272, 1070, 1026, 991, 932, 851, 702 cm1 ‘H-NMR (400 MHz, DMSO-d6): ö (ppm) = 2.99-3.07 (m, 1H), 3.15-3.24 (m, 5H), 5.05 (d, 1H), 6.24 (s, 1H), 7.28-7.40 (m, 5H), 7.54 (d, J=8.2 Hz, 2H), 8.16 (d, J=8.2 Hz, 2H), 9.4 (br s, 2H); ‘3C-NMR (400 MHz, DMSO-d6): ö (ppm)= 31.4, 47.5, 53.9, 68.5, 123.9, 126.2, 128.0, 128.6, 130.4, 142.1, 146.0, 146.7; MS: mlz=287 (M+H).5Nitrogen protection, -10 C, BH3-THF (1M, 70 mL)Add dropwise to CBS (1M, 3.6mL, ), The dropping time is 30 minutes, and the stirring is completed for 60 minutes.Intermediate I (10 g) was dissolved in THF (50 mL) and added dropwise to the reaction system at -10 C.The dropping time is 60 minutes, the holding reaction is completed for 2 hours after the dropwise addition, and the liquid phase is controlled, and the remaining material is less than 1%.Quenched with MeOH (10 mL).(100 mL), the organic phase was washed with saturated sodium bicarbonate (100 mL) and brine (100 mL)Dry, concentrate, add 20mL t-butanol to dissolve, Slowly add 3.2 mL of concentrated hydrochloric acid.The mixture was stirred and tempered at room temperature for 12 h, filtered, washed with 10 mL of t-butyl alcohol, and dried to give 9.6 g of solid.which isLabelonIntermediate (R)-2-(4-nitrophenethyl)amino)-1-phenylethanol hydrochloride, yield 85%, The chemical purity is 99.57%, and the chiral purity is 99.61%.100.0 gm (0.342 mol) of (R)-(-)-1-phenyl-1, 2-ethanediol 2-tosylate of formula (12)and 170.6 gm (1.026 mol) of 4-nitrophenylethylamine of formula (13) and 300m1 of tetrahydrofuran (THF) were charged in a clean and dry round bottom flask and stined. The resultant reaction mixture was heated to about 60C and stirred for about 18 hours. The reaction progress was monitored by TLC, after completion of reaction, reaction mass was cooled to about 30C. The solid precipitated was filtered and the solid was washed with200m1 of tetrahydrofuran (THF). The filtrates were combined and distilled off under reduced pressure to afford the syrup. The resultant syrup was suspended in 300m1 of methyl tertiary butyl ether (MTBE) and treated with 13% w/w (144.2 gm (0.5 13 mol) of IPA/HC1 (HC1 gas suspended in isopropyl alcohol) for about 1 hour at about 25-35C. The separated solid was filtered and the solid was washed with MTBE followed by slurry wash with water. The solidobtained was dried till to get constant weight to yield 70 gms of (R)-1-Phenyl-2-[[2-(4- nitrophenyl)ethyl] aminojethanol hydrochloride of formula (2) as crystalline solid.M.P: 194.1-197.4C; SOR: [11125: -35 (c=0.5 in MeOH);FTIR (KBr): 3542, 2990, 2442, 1607, 1598, 1522, 1441, 1347, 1315, 1272, 1070, 1026, 991, 932, 851, 702 cm1 'H-NMR (400 MHz, DMSO-d6): oe (ppm) = 2.99-3.07 (m, 1H), 3.15-3.24 (m, 5H), 5.05 (d, 1H), 6.24 (s, 1H), 7.28-7.40 (m, 5H), 7.54 (d, J=8.2 Hz, 2H), 8.16 (d, J=8.2 Hz, 2H), 9.4 (br s, 2H); '3C-NMR (400 MHz, DMSO-d6): oe (ppm)= 31.4, 47.5, 53.9, 68.5, 123.9, 126.2, 128.0, 128.6, 130.4, 142.1, 146.0, 146.7; MS: mlz=287 (M+H).5100.0 gm (0.342 mol) of (R)-(-)-1-phenyl-1, 2-ethanediol 2-tosylate of formula (12)and 170.6 gm (1.026 mol) of 4-nitrophenylethylamine of formula (13) and 300m1 of tetrahydrofuran (THF) were charged in a clean and dry round bottom flask and stined. The resultant reaction mixture was heated to about 60C and stirred for about 18 hours. The reaction progress was monitored by TLC, after completion of reaction, reaction mass was cooled to about 30C. The solid precipitated was filtered and the solid was washed with200m1 of tetrahydrofuran (THF). The filtrates were combined and distilled off under reduced pressure to afford the syrup. The resultant syrup was suspended in 300m1 of methyl tertiary butyl ether (MTBE) and treated with 13% w/w (144.2 gm (0.5 13 mol) of IPA/HC1 (HC1 gas suspended in isopropyl alcohol) for about 1 hour at about 25-35C. The separated solid was filtered and the solid was washed with MTBE followed by slurry wash with water. The solidobtained was dried till to get constant weight to yield 70 gms of (R)-1-Phenyl-2-[[2-(4- nitrophenyl)ethyl] aminojethanol hydrochloride of formula (2) as crystalline solid.M.P: 194.1-197.4C; SOR: [11125: -35 (c=0.5 in MeOH);FTIR (KBr): 3542, 2990, 2442, 1607, 1598, 1522, 1441, 1347, 1315, 1272, 1070, 1026, 991, 932, 851, 702 cm1 'H-NMR (400 MHz, DMSO-d6): oe (ppm) = 2.99-3.07 (m, 1H), 3.15-3.24 (m, 5H), 5.05 (d, 1H), 6.24 (s, 1H), 7.28-7.40 (m, 5H), 7.54 (d, J=8.2 Hz, 2H), 8.16 (d, J=8.2 Hz, 2H), 9.4 (br s, 2H); '3C-NMR (400 MHz, DMSO-d6): oe (ppm)= 31.4, 47.5, 53.9, 68.5, 123.9, 126.2, 128.0, 128.6, 130.4, 142.1, 146.0, 146.7; MS: mlz=287 (M+H).5To a stirred solution of 2-(4-Nitro-phenyl)-ethylamine hydrochloride (NPA HCI) (100.0 g) in water (600 mL); triethylamine (55.0 g) and catalytic amount of tetra-butyl ammonium bromide (TBAB) was added at 28C (±2). To this solution, R-styrene oxide (77.05 g) was added and temperature of the solution was raised to 42C (±2) and maintained it at this temperature for 3 hrs. The reaction mass was cooled to 28C (±2) and diluted with dichloromethane (600 mL). The organic layer was separated and concentrated under vacuo. To the obtained residue, tetrahydrofuran (200 mL) was added and the solution cooled to 10C. To this cooled mixture, solution of hydrochloric acid in isopropanol (17%, 100 mL) was added. The precipitated solid was stirred, filtered, washed it with tetrahydrofuran and dried it under vacuo at 40C to obtain (R)-2-[2 ?-(4-nitrophenyl)ethyl]amino]- I -phenylethanol monohydrochloride.Yield: 38.3 g (24.05%); Purity by HPLC: 96.5 %.Compound I (15g, 0.0465mol) in 150ml of methanol was added with stirring, ammonium formate (14.6g, 0.2325mol), 1.5g10% palladium on carbon, followed by stirring warmed to 65 , refluxed for 5h.TLC monitoring (GF254TLC plate, developing solvent: ethyl acetate: methanol = 5) to compound I fluorescence spots disappear.Concentrated under reduced pressure to remove methanol, water and ethyl acetate.Ethyl acetate was evaporated under reduced pressure to give an off-white solid (II): 10.91g, yield 91.71%Example-4: Preparation of (R)-2-[[2-(4-aminophenyl)ethyl]-amino]-l-phenylethanoI (FormuIa-6) Iron powder (86.8 gms) was added to a mixture of (R)-2-[[2'-(4-nitrophenyl)- ethyl] amino] -1 -phenylethanol monohydrochloride compound of formula-5a (100 gms), tetrahydrofuran (500 ml) and water (500 ml) at 25-30C and stirred for 15 min at the same temperature. Slowly added hydrochloric acid (124 ml) to the reaction mixture at 25-30C and stirred for 12 hrs at the same temperature. After completion of the reaction, water was added to the reaction mixture at 25-30C. Cooled the reaction mixture to 10-20C and the pH of the reaction mixture was adjusted to 9.0 using aqueous sodium hydroxide solution. Ethyl acetate was added to the reaction mixture and stirred for 30 mins. Both the organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate. Distilled off the solvent from the organic layer and co-distilled with cyclohexane. 300 ml of cyclohexane was added to the obtained compound, heated the reaction mixture to reflux temperature and stirred for 30 mins at the same temperature. Cooled the reaction mixture to 25-30C and stirred for 90 mins at the same temperature. Filtered the precipitated solid, washed with cyclohexane and dried to get the title compound. Yield: 70.0 gmsA mixture of (100 g) (R)-2-[2' -(4-nitrophenyl)ethyl]amino] -1 -phenylethanol monohydroch bride (prepared according to example Ib), methanol (2000 mL) and Raney Nickel (20 g, wet) was stirred under hydrogen pressure (60 psi) for 6 hrs. The reaction solution was filtered, and the filtrate was concentrated in vacuo. The residue was mixed with isopropanol (300 mL) and reaction mixture was heated to 78C (±2). The mixture was added to toluene (900 mL). The reaction mixture was gradually cooled to 28C (±2) and stirred at this temperature for 3 hrs. The solid obtained was filtered, washed with toluene and dried under vacuo at 48C (±2) to obtain (R)-2-[[2-(4-aminophenyl)ethyl]-amino]- I -phenylethanol monohydrochioride.Yield: 78.1 g (86.1%); Purity by HPLC: 99.14 %.A mixture of 11.0 kg of A mixture of 11.0 kg of Example-3: Preparation of (R)-2-[}2-(4-aminophenyl)ethyI]-amino]-l-phenyIethanoI monohydrochloride (or) (R)-2-(4-aminophenethylamino)-l-phenylethanol mono hydrocloride (FormuIa-6a) (R)-2-[[2'-(4-nitrophenyl)-ethyl]amino]- 1 -phenylethanol monohydrochloride compound of formula-5a (50 gms), methanol (500 ml) and 5% Pd/C (5 gm) were charged into an autoclave vessel. 4-5 kg/cm hydrogen gas pressure was applied to the reaction mixture at 45-50C and stirred for 6 hrs at the same temperature and pressure. Cooled the reaction mixture to 25-30C and filtered through hyflo bed. Distilled off the solvent completely from the filtrate under reduced pressure and co-distilled with cyclohexane. 150 ml of cyclohexane was added to the obtained compound, heated the reaction mixture to reflux temperature and stirred for 45 min at the same temperature. Cooled the reaction mixture to 25-30C and stirred for 45 mins at the same temperature. Filtered the precipitated solid, washed with cyclohexane and dried to get the title compound. Yield: 35.0 gms.Method-Ca?): 88.0 gm of (R)- 1 -Phenyl-2- [ [2-(4-nitrophenyl)ethyl] amino] ethanolhydrochloride of formula (2) obtained in step-I was dissolved in 1320 ml of methanol and transfened into hydrogenator vessel containing 8.8 gms of Raney-nickel. The resultantreaction suspension was agitated under 6 kg/cm2 to 8 kg/cm2 hydrogen gas pressure at about45C for about 8 hours. The reaction progress was monitored by TLC (thin layer chromatography). After completion of reaction, reaction mass was cooled to about 30C, the reaction suspension was filtered on celite bed to separate the catalyst and washed with methanol. The filtrates were combined and concentrated under reduced pressure to givecrude product as liquid. The resulting crude product was suspended in 260 ml of ethyl acetate and stined for about 1 hour at about 30C. The solid separated was filtered and the solid obtained was washed with ethyl acetate followed by drying the solid to yield 72 gms of (R)- 1 -phenyl-2- [ [2-(4-aminphenyl)ethyl] amino] ethanol monohydrochloride of formula (10) as crystalline solid.SOR: []25 -38.7 (c=0.5 in MeOH);FTIR(KBr):3357, 3391, 2956, 1612, 1519, 1449, 1406, 1272, 1098, 1052, 924, 821, 756, 699 cm1 'H-NMR (400 MHz, DMSO-d6): oe (ppm) = 2.84-2.86 (m, 2H), 2.98-3.13 (m, 4H), 5.03 (d, 3H), 6.22 (s, 1H), 6.51 (d, J=7.5 Hz, 2H), 6.86 (d, J=7.5 Hz, 2H), 7.28-7.37 (m, 5H), 9.3 (br s, 2H).?3C-NMR (400 MHz, DMSO-d6): oe (ppm)= 30.9, 48.9, 53.9, 68.5, 114.5, 124.4, 126.2, 128.0, 128.6, 129.3, 142.2, 147.5.MS: mlz=257 (M+H).To a stirred solution of (100 g) (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (prepared according to example la) in tetrahydrofuran (400 mL), sodium borohydride (44.07 g) was added at 28C (±2). After addition of sodium borohydride, the reaction temperature was lowered to 2C (±2). To this chilled mass, solution of iodine (169.03 g) in tetrahydrofuran (600 mL) was added slowly. Thereafter temperature was increased to reflux and mixture was stirred for 10 hrs. The reaction mixture was cooled to 5C (±2), to which then methanol (50 mL) was added and stirred for 30 minutes. Conc. hydrochloric acid aqueous solution (35%, 20.83 mL) was added slowly while maintaining exotherm below 10C and the mixture was stirred for 30 minutes. The reaction mixture was allowed to warm to the 28C (±2), water was added follOwed by heating the reaction mass at 68C (±2) for 1 hr. Tetrahydrofuran and methanol were distilled under vacuo. The reaction mixture was cooled to 30C (±2) and it was diluted with dichloromethane (800 mL) and aqueous ammonia solution (200 mL). To the organic layer, solution of hydrochloric acid in isopropanol (17%, 100 mL) was added slowly and stirred it for 3 hrs. The solid obtained was filtered, washed with dichloromethane (100 mL) and dried under vacuo at 48C (±2) to obtain (R)-2-[2?-(4-nitrophenyl)ethyl]amino]-1-phenylethanol monohydrochioride.Yield: 94.8 g (90.5%); Purity by HPLC: 99.09%.The intermediate (M-01) (9 g, 30 mmol, 1 eq)And NaBH4 (3.45 g, 90 mmol, 3 eq) were dissolved in dry THF (60 mL)Et2O · BF3 (11.7 mL, 90 mmol, 3 eq, w = 46.5%) was slowly added dropwise under ice-Dripping finished insulation reaction for 20 minutes, returned to room temperature, reflux 3-4h, TLC tracking or liquid phase control reaction is completed, returned to room temperature, The solvent was concentrated in vacuo 70% solvent, THF was recovered, Ice bath slowly dropping 1mol / L dilute hydrochloric acid (30mL) quenching reaction, And then concentrated NaOH solution to the system to alkaline (pH ' 9), Extracted with ethyl acetate 2-3 times, The organic phase was washed with saturated NaHCO3, dried and concentrated to an oil.The oil was dissolved in isopropanol at 50 C, Slowly dropwise 12 mol / L concentrated hydrochloric acid (3 mL, 1.2 eq) to precipitate a white solid, Low temperature crystallization 1h, filtration, washing with isopropyl alcohol products, The hydrochloride salt of the intermediate (M-02) was dried, Purity 99.83% (HPLC) in 90% yield.Compound III (20g, 0.0666mol) in 60ml1, 3--dimethyl-2-imidazolidinone and tetrahydrofuran, was added dropwise 133.2ml1mol / L borane-tetrahydrofuran solution together, 70 refluxed 4h.TLC monitoring (GF254TLC plate, developing solvent: ethyl acetate) to compound III phosphor dots disappear.Methanol and concentrated hydrochloric acid was added dropwise, washed with aqueous potassium carbonate, water and ethyl acetate.Ethyl acetate was removed by concentration under reduced pressure, isopropanol, concentrated hydrochloric acid was recrystallized from a pale yellow solid (I): 17.73g, yield 82.35%.A mixture of 7.51 kg of (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide, 23 L of 1, 3-dimethyl-2-imidazolidinone and 23 L of tetrahydrofuran was cooled to -18C, to which was then dropped 49.4 kg of 1M borane-tetrahydrofuran solution at not higher than -7C. Thereafter, the temperature was increased to 70C, and the mixture was stirred for 5 hours. The reaction mixture was cooled to -12C, to which were then added 2.9 kg of methanol and 5.9 kg of concentrated hydrochloric acid at not higher than 5C. The mixture was stirred at 68C for one hour and concentrated in vacuo such that the inner volume became 50 L. 60 kg of 30 % K2CO3 aqueous solution and 6 L of water were added, and the mixture was extracted with 75 L of ethyl acetate. The organic layer was washed with 75 L and concentrated in vacuo. The residue was added with and dissolved in 75 L of isopropanol at 40C, and the solution was crystallized from 2.46 kg of concentrated hydrochloric acid, followed by stirring at 23C overnight. A crystal was collected by filtration and washed with 38 L of isopropanol, followed by drying in vacuo. There was thus obtained 7.29 kg of A mixture of 7.51 kg of (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide, 23 liters of 1, 3-dimethyl-2-imidazolidinone and 23 liters of tetrahydrofuran was cooled at -18C and 49.4 kg of 1M boran-tetrahydrofuran solution was dropped thereinto at not higher than -7C. After that, temperature of the mixture was raised to 70C followed by stirring for 5 hours. The reaction mixture was cooled at -12C and 2.9 kg of methanol and 5.9 kg of concentrated hydrochloric acid were added thereto at not higher than 5C. After stirring at 68C for 1 hour, the mixture was concentrated in vacuo until the amount became 50 liters. A 30% aqueous solution (60 kg) of K2CO3 and 6 liters of water were added thereto followed by extracting with 75 liters of ethyl acetate. The organic layer was washed with 75 liters of water and concentrated in vacuo. Isopropanol (75 liters) was added to the residue, the mixture was dissolved at 40C and 2.46 kg of concentrated hydrochloric acid was added to crystallize followed by stirring at 23C throughout one night. The crystals were filtered and washed with 38 liters of isopropanol. They were dried in vacuo to give 7.29 kg of (R)-2-[[2-(4- nitrophenyl)ethyl]amino]-1-phenylethanol monohydrochloride. 1H-NMR (DMSO-d6, 400 MHz) delta (ppm) = 3.00-3.08 (1H, m), 3.15-3.30 (5H, m), 5.00-5.05 (1H, m), 6.23 (1H, d, J = 4.0 Hz), 7.29-7.35 (1H, m), 7.36-7.43 (4H, m), 7.57 (2H, d, J = 8.4 Hz), 8.21 (2H, d, J = 8.4 Hz), 9.12 (2H, br). FAB-MS m/z: 287 (M+H)+.Example-2: Preparation of (R)-2-[[2'-(4-nitrophenyl)-ethyl]amino]-l-phenyIethanol mono hydrochloride (or) (R)-2-(4-nitrophenethylamino)-l-phenylethanol mono hydrochloride (Formula-5a) Borane-dimethyl sulfide (500 ml) was added to a solution of (R)-2-hydroxy-N-[2-(4-nitro phenyl)ethyl]-2-phenylacetamide compound of formula-4 (100 gms) in tetrahydrofuran (300 ml) at -10C to -5C and stirred for 45 mins at the same temperature. Slowly heated the reaction mixture to 70-75C and stirred for 5 hrs at the same temperature. Cooled the reaction mixture to 0-5C and quenched the reaction mixture by adding methanol (38.6 ml) and hydrochloric acid (78.5 ml) and stirred for 15 mins at the same temperature. Slowly heated the reaction mixture to 65-70C and stirred for 90 mins at the same temperature. Distilled off the 50% of the solvent from the reaction mixture under reduced pressure. 30% aqueous potassium carbonate solution (800 ml), water (80 ml) and ethyl acetate (1000 ml) were added to the reaction mixture. Both the organic and aqueous layers were separated and distilled off the solvent completely from the organic layer under reduced pressure. Isopropanol (1000 ml) was added to the obtained compound and heated the reaction mixture to 35-40C. Hydrochloric acid (32.7 gms) was added to the reaction mixture at 25-30C and stirred for 15 hrs at the same temperature. Filtered the precipitated solid, washed with isopropanol and dried to get the title compound. Yield: 97.0 gms.

Molecular Weight:322.78
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:6
Exact Mass:322.1084202
Monoisotopic Mass:322.1084202
Topological Polar Surface Area:78.1
Heavy Atom Count:22
Complexity:305
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes