115290-81-8

Basic information

• Product Name: (R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL
• Synonyms: (R)-3-(methylamino)-1-phenylpropanol;(1R)-(+)-3-(Methylamino)-1-phenylpropan-1-ol;(3R)-N-Methyl-3-hydroxy-3-phenylpropylamine;(R)-3-Hydroxy-N-methyl-3-phenylpropylamine;(R)-N-Methyl-3-hydroxy-3-phenylpropylamine;(R)-N-Methyl-3-phenyl-3-hydroxypropylamine;Atomoxetine Related Compound A (10 mg) (3-(Methylamino)-1-phenylpropan-1-ol);Destolyl Atomoxetine
• CAS NO: 115290-81-8
• Molecular Formula: C₁₀H₁₅NO
• Molecular Weight: 165.23
• Mol File: 115290-81-8.mol

Chemical Properties

• Boiling Point: 286℃
• Flash Point: 115℃
• Appearance: /
• Density: 1.017
• Vapor Pressure: 0.00126mmHg at 25°C
• Refractive Index: 1.53
• PKA: 14.24±0.20(Predicted)
• CAS DataBase Reference: (R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL(115290-81-8)
• EPA Substance Registry System: (R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL(115290-81-8)

Safety Data

• Hazardous Substances Data: 115290-81-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL is used as an intermediate in the synthesis of various pharmaceutical compounds, particularly those targeting the central nervous system. Its unique structure allows for the development of drugs with specific mechanisms of action, such as norepinephrine reuptake inhibitors.
Used in Chemical Industry:
(R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL is used as a key building block in the synthesis of various chemical compounds, including those with potential applications in materials science, agrochemicals, and other specialty chemicals. Its versatility in chemical reactions and ability to form stable derivatives make it a valuable asset in the development of new products and technologies.
Used in Research and Development:
(R)-(+)-3-(N-METHYLAMINO)-1-PHENYL-1-PROPANOL is also used in research and development settings, where its unique properties can be explored for potential applications in various fields. This includes the development of new drugs, the study of biological interactions, and the creation of novel materials with specific properties.

InChI:InChI=1/C10H15NO/c1-11-8-7-10(12)9-5-3-2-4-6-9/h2-6,10-12H,7-8H2,1H3/t10-/m1/s1

Synthetic route

(R)-3-iodo-1-phenyl-1-propanol (127073-84-1) + methylamine (74-89-5) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
In tetrahydrofuran; water at 23℃; for 2h;	99%
In tetrahydrofuran; water at 25℃; for 12h; Inert atmosphere; enantioselective reaction;	98%
In tetrahydrofuran; water at 20℃;	85%

(R)-(3-hydroxy-3-phenylpropyl)carbamic acid ethyl ester (502697-62-3) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating;	93%
With lithium aluminium tetrahydride In tetrahydrofuran Heating;	89%

β-Methylaminoethyl phenyl ketone hydrochloride (2538-50-3) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With Rh[((R,R)-BenzP*)(cod)]SbF6; hydrogen; caesium carbonate; zinc(II) chloride In methanol at 20℃; under 19001.3 Torr; for 48h; Autoclave; enantioselective reaction;	93%
Multi-step reaction with 2 steps 1: potassium borohydride / tetrahydrofuran / 66 °C 2: sodium hydrogencarbonate / chloroform; water View Scheme

(1R) 3-phenyl-3-hydroxypropyl methanesulfonate (115290-78-3) + methylamine (74-89-5) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
In tetrahydrofuran; water at 65℃; for 24h;	91%
In tetrahydrofuran; water at 60 - 65℃; for 4h;	80%
In tetrahydrofuran; water at 65℃; for 3h;	837 mg

N-methyl-3-phenylprop-2-en-1-amine (60960-88-5) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Stage #1: N-methyl-3-phenylprop-2-en-1-amine With L-diisopinocampheylborane In 1,2-dimethoxyethane at 30℃; for 2h; Stage #2: With dihydrogen peroxide; potassium hydroxide In 1,2-dimethoxyethane at 20℃; for 2h;	90.67%

(R)-6-phenyl-1,3-oxazinan-2-one R-7a (406218-18-6) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran Heating;	90%

(3R)-3-phenyl-3-hydroxypropionic acid methyl amide → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 6h; Reflux;	86%

Phenyl vinyl ketone (768-03-6) + methylamine (74-89-5) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Stage #1: Phenyl vinyl ketone; methylamine With sodium carbonate In water; isopropyl alcohol at 20℃; for 2h; Inert atmosphere; Stage #2: With chloro[(1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]-(mesitylene) ruthenium (II); sodium formate In water; isopropyl alcohol at 40℃; for 10h; pH=7; Inert atmosphere; enantioselective reaction;	79%

(1R)-3-chloro-1-phenylpropanol (100306-33-0) + methylamine (74-89-5) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With potassium iodide In methanol; water at 80℃; for 8h;	72%
With sodium iodide In water

3-methylamino-1-phenyl-propan-1-ol; hydrochloride (57256-92-5) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Stage #1: 3-methylamino-1-phenyl-propan-1-ol; hydrochloride With sodium hydrogencarbonate In chloroform; water Stage #2: With (S)-Mandelic acid In acetone	46%

((R)-3-Hydroxy-3-phenyl-propyl)-carbamic acid methyl ester → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran Heating;

(R)-3-(N-benzyl-N-methylamino)-1-phenylpropanol hydrochloride → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol for 20h; Ambient temperature; Yield given;

methylamine (74-89-5) + 3-hydroxy-3-phenylpropyl 4-methylbenzenesulfonate (51699-49-1) → (S)-N-methyl-3-amino-1-phenyl-1-propanol (114133-37-8) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Stage #1: 3-hydroxy-3-phenylpropyl 4-methylbenzenesulfonate With 3 A molecular sieve; oxygen; (-)-sparteine; palladium diacetate In toluene at 80℃; under 760 Torr; for 36h; Stage #2: methylamine With water In tetrahydrofuran at 65℃;

(6R)-2-((S)-1-triisopropylsilyloxyethyl)-3-methyl-6-phenyl-1,3-oxazinane (823182-36-1) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
With hydrogenchloride In methanol; water at 90℃; for 1.5h;

Benzoylacetonitrile (614-16-4) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 74 percent / borane-dimethylsulfide complex; polymer-supported chiral sulfonamide / tetrahydrofuran / Heating 2: sodium hydrogen carbonate / CH2Cl2; H2O / 2 h / 20 °C 3: 93 percent / lithium aluminum hydride / tetrahydrofuran / 2 h / Heating View Scheme

(1R)-3-amino-1-phenyl-1-propanol (138750-31-9) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogen carbonate / CH2Cl2; H2O / 2 h / 20 °C 2: 93 percent / lithium aluminum hydride / tetrahydrofuran / 2 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 88 percent / K2CO3 / CH2Cl2; H2O / 20 °C 2: 89 percent / LiAlH4 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 2 steps 1: NaHCO3 / tetrahydrofuran 2: LiAlH4 / tetrahydrofuran / Heating View Scheme

butyric acid 2-ethoxycarbonyl-1-phenyl-ethyl ester (118856-08-9) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: Candida rugosa lipase; MgCl2 / H2O; diisopropyl ether / 24 h / 30 °C 2: 92 percent / LiAlH4 / tetrahydrofuran / 1 h / 20 °C 3: 85 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C / cooling 4: 80 percent / tetrahydrofuran; H2O / 4 h / 60 - 65 °C View Scheme

Ethyl 3-hydroxy-3-phenylpropanoate (5764-85-2) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: DCC; 4-(dimethylamino)pyridine / CH2Cl2 / 20 °C 2: Candida rugosa lipase; MgCl2 / H2O; diisopropyl ether / 24 h / 30 °C 3: 92 percent / LiAlH4 / tetrahydrofuran / 1 h / 20 °C 4: 85 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C / cooling 5: 80 percent / tetrahydrofuran; H2O / 4 h / 60 - 65 °C View Scheme
Multi-step reaction with 3 steps 1.1: 85 percent / lithium aluminum hydride / tetrahydrofuran / 2 h 2.1: 95 percent / Et3N / CH2Cl2 / 0 h / -10 °C 3.1: O2; (-)-sparteine; 3 Angstroem sieves / Pd(OAc)2 / toluene / 36 h / 80 °C / 760 Torr 3.2: H2O / tetrahydrofuran / 65 °C View Scheme

ethyl (R)-3-hydroxy-3-phenylpropanoate (72656-47-4) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / LiAlH4 / tetrahydrofuran / 1 h / 20 °C 2: 85 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C / cooling 3: 80 percent / tetrahydrofuran; H2O / 4 h / 60 - 65 °C View Scheme
Multi-step reaction with 3 steps 1: 86 percent / LiAlH4 / tetrahydrofuran; diethyl ether / 1.5 h / 0 - 20 °C 2: 82 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C 3: 91 percent / tetrahydrofuran; H2O / 24 h / 65 °C View Scheme

(R)-3-phenyl-1,3-dihydroxypropane (103548-16-9) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C / cooling 2: 80 percent / tetrahydrofuran; H2O / 4 h / 60 - 65 °C View Scheme
Multi-step reaction with 2 steps 1: 82 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C 2: 91 percent / tetrahydrofuran; H2O / 24 h / 65 °C View Scheme
Multi-step reaction with 2 steps 1: 74 percent / triethylamine / diethyl ether / 3 h / -10 - 0 °C 2: 837 mg / H2O; tetrahydrofuran / 3 h / 65 °C View Scheme

benzaldehyde (100-52-7) + SASRIN-maleidobenzoic acid resin → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: LDA / tetrahydrofuran; hexane / 1 h / -78 °C 1.2: tetrahydrofuran; hexane / 1 h / -78 °C 2.1: DCC; 4-(dimethylamino)pyridine / CH2Cl2 / 20 °C 3.1: Candida rugosa lipase; MgCl2 / H2O; diisopropyl ether / 24 h / 30 °C 4.1: 92 percent / LiAlH4 / tetrahydrofuran / 1 h / 20 °C 5.1: 85 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C / cooling 6.1: 80 percent / tetrahydrofuran; H2O / 4 h / 60 - 65 °C View Scheme

(6R)-2-((S)-1-triisopropylsilyloxyethyl)-6-phenyl-1,3-oxazinan-4-one → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium hexamethyldisilazide / tetrahydrofuran / 2 h / 20 °C 2: diphenyl silane / tris(triphenylphosphine)rhodium(I) carbonyl hydride / tetrahydrofuran / 15 h / 20 °C 3: HCl / methanol; H2O / 1.5 h / 90 °C View Scheme

(6R)-2-((S)-1-triisopropylsilyloxyethyl)-3-methyl-6-phenyl-1,3-oxazinan-4-one (823182-35-0) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: diphenyl silane / tris(triphenylphosphine)rhodium(I) carbonyl hydride / tetrahydrofuran / 15 h / 20 °C 2: HCl / methanol; H2O / 1.5 h / 90 °C View Scheme

styrene oxide (96-09-3) + 1-chloro-1-phenylethene, 1,2-dichloro-1-phenyl-ethane, benzaldehyde, benzoic acid → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: 80 percent / ethanol; H2O / 20 °C 2: 46 percent / Pseudomonas cepacia lipase on modified ceramic particles / diisopropyl ether / 16 h / 27 °C 3: 88 percent / BH3*SMe2 / tetrahydrofuran / Heating 4: 88 percent / K2CO3 / CH2Cl2; H2O / 20 °C 5: 89 percent / LiAlH4 / tetrahydrofuran / Heating View Scheme

3-hydroxy-3-phenylpropanenitrile (73627-97-1, 121617-17-2, 132203-26-0, 17190-29-3) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 46 percent / Pseudomonas cepacia lipase on modified ceramic particles / diisopropyl ether / 16 h / 27 °C 2: 88 percent / BH3*SMe2 / tetrahydrofuran / Heating 3: 88 percent / K2CO3 / CH2Cl2; H2O / 20 °C 4: 89 percent / LiAlH4 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 3 steps 1: hydrogen, NH3 / Raney Ni / ethanol / 90 °C / p(NH3) = 30 psi and p(H2) = 170 psi 2: NaHCO3 / tetrahydrofuran 3: LiAlH4 / tetrahydrofuran / Heating View Scheme

(R)-3-acetyloxy-3-phenylpropanenitrile (198561-42-1) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 88 percent / BH3*SMe2 / tetrahydrofuran / Heating 2: 88 percent / K2CO3 / CH2Cl2; H2O / 20 °C 3: 89 percent / LiAlH4 / tetrahydrofuran / Heating View Scheme

ethyl 3-oxo-3-phenylpropionate (94-02-0) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / H2 / RuBr2((S)-(6,6'-(MeO)2-biphenyl-2,2'-diyl)bis(Ph2-phosphane) / ethanol / 18 h / 50 °C / 760.05 Torr 2: 86 percent / LiAlH4 / tetrahydrofuran; diethyl ether / 1.5 h / 0 - 20 °C 3: 82 percent / Et3N / diethyl ether / 3 h / -10 - 0 °C 4: 91 percent / tetrahydrofuran; H2O / 24 h / 65 °C View Scheme

1-phenyl-1,3-propanediol (4850-49-1) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 95 percent / Et3N / CH2Cl2 / 0 h / -10 °C 2.1: O2; (-)-sparteine; 3 Angstroem sieves / Pd(OAc)2 / toluene / 36 h / 80 °C / 760 Torr 2.2: H2O / tetrahydrofuran / 65 °C View Scheme

3-(benzyl methylamino)-1-phenylpropan-1-one hydrochloride (5409-62-1) → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, 2, (2S,4S)-N-(methylcarbamoyl)-4-(dicyclohexylphosphino)-2-<(diphenylphosphino)methyl>pyrrolidine / methanol / 48 h / 50 °C / 22800 Torr 2: H2 / 5percent Pd/C / ethanol / 20 h / Ambient temperature View Scheme

acetophenone (98-86-2) + sulfur → (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 50 percent / concd. HCl / ethanol / 4 h / Heating 2: H2, 2, (2S,4S)-N-(methylcarbamoyl)-4-(dicyclohexylphosphino)-2-<(diphenylphosphino)methyl>pyrrolidine / methanol / 48 h / 50 °C / 22800 Torr 3: H2 / 5percent Pd/C / ethanol / 20 h / Ambient temperature View Scheme

ortho-methylphenyl iodide (615-37-2) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → atomoxetine hydrochloride (82248-59-7)

Conditions	Yield
Stage #1: ortho-methylphenyl iodide; (R)-N-methyl-3-phenyl-3-hydroxypropylamine With potassium carbonate; copper(l) iodide In toluene at 148℃; for 21h; Ullmann type reaction; Heating / reflux; Stage #2: With hydrogenchloride In water pH=1 - 2; Stage #3: With sodium hydroxide In water pH=11 - 12;	99%
Stage #1: ortho-methylphenyl iodide; (R)-N-methyl-3-phenyl-3-hydroxypropylamine With potassium carbonate; copper(l) iodide In toluene at 148℃; for 21h; Ullmann type reaction; Heating / reflux; Stage #2: With hydrogenchloride In water pH=1 - 2; Stage #3: With sodium hydroxide In water pH=11 - 12;	94%
Stage #1: ortho-methylphenyl iodide; (R)-N-methyl-3-phenyl-3-hydroxypropylamine With potassium phosphate; copper(l) iodide In toluene for 24h; Ullmann type reaction; Heating / reflux; Stage #2: With hydrogenchloride In water pH=1 - 2; Stage #3: With sodium hydroxide In water pH=12 - 14;	82%

4-chlorobenzotrifluoride (98-56-6) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-fluoxetine (54910-89-3, 57226-07-0, 100568-02-3, 100568-03-4)

Conditions	Yield
With sodium hydride In dimethyl sulfoxide at 80 - 90℃; for 1h;	92%
In N,N-dimethyl acetamide	86%
In N,N-dimethyl acetamide	86%

2-Fluorotoluene (95-52-3) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-tomoxetine (105314-52-1, 105314-53-2, 63940-51-2, 83015-26-3)

Conditions	Yield
Stage #1: (R)-N-methyl-3-phenyl-3-hydroxypropylamine With potassium hydroxide In dimethyl sulfoxide at 130℃; for 1h; Stage #2: 2-Fluorotoluene In dimethyl sulfoxide at 130℃;	89.51%
Stage #1: (R)-N-methyl-3-phenyl-3-hydroxypropylamine With sodium hydride In dimethyl sulfoxide for 0.25h; Stage #2: With Potassium benzoate In dimethyl sulfoxide at 50 - 55℃; for 1h; Stage #3: 2-Fluorotoluene In dimethyl sulfoxide at 50 - 120℃; for 6.25 - 7.25h;
With potassium tert-butylate In dimethyl sulfoxide at 60℃; for 8h;

4-Fluorobenzotrifluoride (402-44-8) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-fluoxetine (54910-89-3, 57226-07-0, 100568-02-3, 100568-03-4)

Conditions	Yield
Stage #1: (R)-N-methyl-3-phenyl-3-hydroxypropylamine With sodium hydride In N,N-dimethyl acetamide; paraffin oil at 90℃; for 0.5h; Inert atmosphere; Stage #2: 4-Fluorobenzotrifluoride In N,N-dimethyl acetamide; paraffin oil at 100℃; for 5h; Inert atmosphere;	88%

(R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) + C7H7X → atomoxetine hydrochloride (82248-59-7)

Conditions	Yield
Stage #1: (R)-N-methyl-3-phenyl-3-hydroxypropylamine; C7H7X In ethyl acetate at 77℃; Stage #2: With hydrogenchloride In water; acetone pH=1 - 2;	73%

2-Fluorotoluene (95-52-3) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → rac-tomoxetine hydrochloride

Conditions	Yield
With sodium hydride 1) DMSO, 2) DMSO; Yield given. Multistep reaction;

2-methylchlorobenzene (95-49-8) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-tomoxetine (105314-52-1, 105314-53-2, 63940-51-2, 83015-26-3)

Conditions	Yield
With 2,4-dichlorophenoxyacetic acid dimethylamine; sodium hydride Multistep reaction;

2-Chloroanisole (766-51-8) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-3-(2-methoxyphenoxy)-N-methyl-3-phenylpropan-1-amine (112066-67-8)

Conditions	Yield
With 2,4-dichlorophenoxyacetic acid dimethylamine; sodium hydride Multistep reaction;

ortho-cresol (95-48-7) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → atomoxetine hydrochloride (82248-59-7)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate Yield given. Multistep reaction;

4-chlorobenzotrifluoride (98-56-6) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-fluoxetine hydrochloride (114247-09-5)

Conditions	Yield
With sodium hydride 1) DMSO, 50 deg C, 20 min, 2) DMSO, 90 deg C, 40 min; Yield given. Multistep reaction;
With sodium hydride 1.) N,N-dimethylacetamide, a) 0 deg C, 5 min, b) 70 deg C, 30 min, 2.) N,N-dimethylacetamide, 100 deg C, 3 h; Yield given. Multistep reaction;
With sodium hydride 1,) 0 deg C, then 70 deg C, 30 min; 2.) 2.5 h, 100 deg C; Yield given. Multistep reaction;

Upstream product

• 100306-33-0 (1R)-3-chloro-1-phenylpropanol 
• 74-89-5 methylamine 
• 127073-84-1 (R)-3-iodo-1-phenyl-1-propanol 
• 115290-78-3 (1R) 3-phenyl-3-hydroxypropyl methanesulfonate 
• 406218-18-6 (R)-6-phenyl-1,3-oxazinan-2-one R-7a 
• 51699-49-1 3-hydroxy-3-phenylpropyl 4-methylbenzenesulfonate 
• 502697-62-3 (R)-(3-hydroxy-3-phenylpropyl)carbamic acid ethyl ester 
• 823182-36-1 (6R)-2-((S)-1-triisopropylsilyloxyethyl)-3-methyl-6-phenyl-1,3-oxazinane 
• 614-16-4 Benzoylacetonitrile 
• 138750-31-9 (1R)-3-amino-1-phenyl-1-propanol 
• 118856-08-9 butyric acid 2-ethoxycarbonyl-1-phenyl-ethyl ester 
• 5764-85-2 Ethyl 3-hydroxy-3-phenylpropanoate 
• 72656-47-4 ethyl (R)-3-hydroxy-3-phenylpropanoate 
• 103548-16-9 (R)-3-phenyl-1,3-dihydroxypropane 

Downstream Products

• 82857-40-7 rac-tomoxetine hydrochloride 
• 105314-52-1 (R)-tomoxetine 
• 112066-67-8 (R)-N-methyl-3-(2-methoxyphenoxy)-3-phenyl-1-propanamine 
• 82248-59-7 atomoxetine hydrochloride 
• 54910-89-3 (R)-fluoxetine 
• 114247-09-5 (R)-fluoxetine hydrochloride 
• 1620141-91-4 (R)-N-methyl-N-{3-phenyl-3-[4-trifluoromethyl]phenoxylpropyl}acetamide 
• 1351468-93-3 (R)-N-(3-hydroxy-3-phenylpropyl)-N-methylacetamide 

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The invention belongs to the technical field of medicines, and particularly relates to a preparation method of atomoxetine hydrochloride serving as a medicine for treating attention deficit hyperactivity. According to the invention, commercially available (E)-N-methyl-3-phenyl-2-propylene-1-amine is adopted as a starting material, and addition, substitution and salification are carried out so as to prepare atomoxetine hydrochloride. The preparation method provided by the invention is simple in preparation process, simple and convenient to operate, relatively high in yield and suitable for industrial production, and can provide sufficient bulk drugs for research and development of medicines.

A site isolation-enabled organocatalytic approach to enantiopure γ-amino alcohol drugs

Solid support-enabled site isolation has previously allowed to use paraldehyde as an acetaldehyde surrogate in aldol reactions. However, only electron-poor aldehydes were tolerated by the system. Herein, we show that the temporary conversion of benzaldehyde into η6-benzaldehyde Cr(CO)3 circumvents this limitation. Asymmetric synthesis of (R)-Phenoperidine, as well as formal syntheses of (R)-Fluoxetine and (R)-Atomoxetine, illustrate the benefits of this strategy.

Method for preparation of optically active 3-amino-arylpropan-1-ol derivatives from 3-chloro-1-arylpropan-1-ol derivatives

The present invention relates to a method for preparing an optically active 3-amino-1-arylpropan-1-ol derivative, including the step of making an optically active 3-chloro-1-arylpropan-1-ol compound react with an amine derivative. The method according to the present invention allows direct amination of an optically active 3-chloro-1-arylpropan-1-ol derivative through a single-step reaction. Thus, it is possible to provide a compound functioning as a key intermediate of various optically active molecules through a simple process with high yield, while maintaining the optical purity of the reactant. Therefore, the method may be used for preparing medicines, such as (S)-Duloxetin, (R)-Fluoxetine, (R)- Tomoxetine or (R)- Nisoxetine, with high optical purity by combining the method for preparing an optically active 3-chloro-1-arylpropan-1-ol derivative as a reactant of the method with an additional substitution reaction.(AA) Tomoxetine(BB) Fluoxetine(CC) 3-amino-1-propanol(DD) Nisoxetine(EE) DuloxetineCOPYRIGHT KIPO 2016

Method for preparing atomoxetine hydrochloride

The invention belongs to the technical field of medicines, and particularly relates to a method for preparing atomoxetine hydrochloride which is a medicine for treating attention deficit hyperactivity disorder. The atomoxetine hydrochloride is made of commercially easily available intermediates 3-methylamino-1-propiophenone hydrochloride. The method includes carrying out reduction, salt decomposition, resolving, substitution and salt forming to obtain the atomoxetine hydrochloride. The method has the advantages that technologies for preparing the atomoxetine hydrochloride are simple and stable and are easy and convenient to implement, high in yield and applicable to industrial production, and sufficient raw materials can be provided for research and development of medicines.

HYDROXY ALIPHATIC SUBSTITUTED PHENYL AMINOALKYL ETHER DERIVATIVES

New hydroxy aliphatic substituted phenyl aminoalkyl ether compounds of formula (I), compositions thereof and their use as a medicament in the treatment of nervous system diseases and/or the treatment of developmental, behavioral and/or mental disorders associated with cognitive deficits.

A method for preparing optically active 3-amino-1-phenylpropanol derivatives as an intermediate and a method for preparing optically active pharmaceutical products using the same

The present invention relates to a method for preparing a 3-amino-1-phenylpropanol derivative having (R) or (S) optical activity with 80% or more of an enantiomeric excess (ee), which includes a step of performing an asymmetric reduction reaction in the presence of a spiroborate ester catalyst and a hydrogen donor. The invention also relates to a method for preparing an optically active pharmaceutical product, which includes a step of preparing a (R)- or (S)-3-amino-1-phenylpropanol derivative, that is an intermediate, by using the catalyst.(AA) 3-amino-1-phenylpropanol(BB) Tomoxetine(CC) Nisoxetine(DD) FluoxetineCOPYRIGHT KIPO 2016

ZnCl2-promoted asymmetric hydrogenation of β-secondary-amino ketones catalyzed by a P-chiral rh-bisphosphine complex

A new catalytic system has been developed for the asymmetric hydrogenation of β-secondary-amino ketones using a highly efficient P-chiral bisphosphine-rhodium complex in combination with ZnCl2 as the activator of the catalyst. The chiral γ-secondary-amino alcohols were obtained in 90-94% yields, 90-99% enantioselectivities, and with high turnover numbers (up to 2000 S/C; S/C = substrate/catalyst ratio). A mechanism for the promoting effect of ZnCl2 on the catalytic system has been proposed on the basis of NMR spectroscopy and HRMS studies. This method was successfully applied to the asymmetric syntheses of three important drugs, (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine, in high yields and with excellent enantioselectivities.

Copper(ii)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: Asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.