116539-55-0

Basic information

• Product Name: 3-Methylamino-1-(2-thienyl)-1-propanol
• Synonyms: (1S)-(-)-3-(MethylaMino)-1-(thien-2-yl)propan-1-ol;(S)-α-[2-(MethylaMino)ethyl]-2-thiopheneMethanol;N-Meth;(S)-2-[3-(Methylamino)-1-hydroxypropyl]thiophene;N-Methyl-3-hydroxy-3-(2-thienyl)-3-aMinopropane;(S)-3-METHYLAMINO-1-(THIOPHENE-2-YL)-PROPAN-1-OL;Duloxetine EP IMpurity B;2-ThiopheneMethanol, a-[2-(MethylaMino)ethyl]-, (aS)-
• CAS NO: 116539-55-0
• Molecular Formula: C₈H₁₃NOS
• Molecular Weight: 171.26
• EINECS: 1533716-785-6
• Product Categories: Amines;Aromatics;Heterocycles
• Mol File: 116539-55-0.mol
• Article Data: 48

Chemical Properties

• Melting Point: 72.0 to 76.0 °C
• Boiling Point: 294.288 °C at 760 mmHg
• Flash Point: 131.781 °C
• Appearance: /
• Density: 1.128 g/cm³
• Vapor Pressure: 0.001mmHg at 25°C
• Refractive Index: 1.553
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 13.77±0.20(Predicted)
• CAS DataBase Reference: 3-Methylamino-1-(2-thienyl)-1-propanol(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Methylamino-1-(2-thienyl)-1-propanol(116539-55-0)
• EPA Substance Registry System: 3-Methylamino-1-(2-thienyl)-1-propanol(116539-55-0)

Safety Data

• Hazardous Substances Data: 116539-55-0(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 116539-55-0 differently. You can refer to the following data:
1. A Duloxetine intermediate. Duloxetine EP Impurity B.
2. A Duloxetine intermediate.

InChI:InChI=1/C8H13NOS/c1-9-5-4-7(10)8-3-2-6-11-8/h2-3,6-7,9-10H,4-5H2,1H3

Synthetic route

C8H13NO2S (1035456-55-3) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
Stage #1: C8H13NO2S With acetic acid; zinc In water at 50℃; for 1.5h; Stage #2: With sodium hydroxide In water	100%

(S)-3-hydroxy-N-methyl-3-(thiophen-2-yl)propanamide (603959-56-4) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With borane-THF In tetrahydrofuran at 20℃; for 4h; Reagent/catalyst;	98%
Stage #1: (S)-3-hydroxy-N-methyl-3-(thiophen-2-yl)propanamide With sodium tetrahydroborate; iodine In tetrahydrofuran at 20℃; for 4.33333h; Heating / reflux; Stage #2: With sodium hydroxide; water In tetrahydrofuran; water; butanone at 64℃; for 0.333333h;	91%
With lithium aluminium tetrahydride In tetrahydrofuran Heating / reflux;	80%

methylamine (74-89-5) + (S)-3-hydroxy-3-(2-thienyl)propyl methanesulfonate (556801-68-4) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
In tetrahydrofuran; water at 65℃; for 3h;	94%

N-methyl-3-(thien-2-yl)-3-morpholino-propylamine hydrochloride → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With Rh[((S,S)-BenzP*)(cod)]SbF6; hydrogen; caesium carbonate; zinc(II) chloride In methanol at 20℃; under 19001.3 Torr; for 20h; Reagent/catalyst; Solvent; Autoclave; enantioselective reaction;	94%
With hydrogen; potassium carbonate; [Rh{(SC,RP)-duanphos}(norbornadiene)]SbF6 In methanol at 20℃; under 7500.6 Torr; for 12h;	93%
With [Rh((S,S)-QuinoxP*)(cod)]SbF6; potassium tert-butylate; hydrogen; zinc(II) iodide In tetrahydrofuran at 25℃; under 15001.5 Torr; for 12h; Reagent/catalyst; enantioselective reaction;	83%

(S)-3-(N-trifluoroacetyl-N-methyl)amino-1-(2-thienyl)propan-1-ol (1204210-39-8) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With water; sodium carbonate In methanol at 20℃; for 4h;	94%

(S)-[3-methoxy(methyl)amino]-1-(2-thienyl)propan-1-ol (1146978-94-0) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With hydrogen; Raney-nickel In methanol at 50℃; for 12h; Autoclave;	90.8%
Raney-nickel In methanol at 50℃; for 12h; Autoclave;

((S)-3-Hydroxy-3-thiophen-2-yl-propyl)-carbamic acid ethyl ester (597581-29-8) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 1.5h; Heating;	88%

salt of (S)-(-)-3-N-methylamino-1-(2-thienyl)-1-propanol and (-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With sodium hydroxide In dichloromethane; water for 0.25h; Product distribution / selectivity;	87%

(S)-3-chloro-1-(thiophen-2-yl)propan-1-ol (164071-56-1) + methylamine (74-89-5) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With chloro-trimethyl-silane In methanol; water at 80℃; for 8h; Reagent/catalyst;	85%

(S)-3-methyl-6-(2-thienyl)-1,3-oxazinan-2-one (654062-24-5) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With water; lithium hydroxide In methanol for 8h; Reflux;	84%

C12H17NO5S → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With methanol; potassium hydroxide at 75℃; for 4h;	83%

phenyl (S)-N-[3-acetoxy-3-(thien-2-yl)propyl]-N-methylcarbamate (625853-22-7) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With methanol; potassium hydroxide at 75℃; for 4h;	83%

S-(-)-3-iodo-1-(2-thienyl)-1-propanol (164071-58-3) + methylamine (74-89-5) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
In tetrahydrofuran; water at 25℃; for 12h; Inert atmosphere;	80%
In tetrahydrofuran; water for 6h; Ambient temperature;	71.5%
In tetrahydrofuran; water at 20℃; for 18h;	71%
In tetrahydrofuran
In tetrahydrofuran; water at 20℃; for 18h;

3-(N-methyl-N-benzylamino)-1-(2-thienyl)-2-propen-1-one (1337865-86-7) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With potassium tert-butylate; hydrogen; [(R)-Binap RuCl2 (R)-DAIPEN] In isopropyl alcohol at 80℃; under 7500.75 Torr; for 16h; Inert atmosphere;	80%

(S)-3-dimethylamino-1-(2-thienyl)propan-1-ol (132335-44-5) + isobutyl chloroformate (543-27-1) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
Stage #1: (S)-3-dimethylamino-1-(2-thienyl)propan-1-ol; isobutyl chloroformate With triethylamine In toluene at 20 - 30℃; for 6h; Stage #2: With potassium hydroxide In methanol at 75℃; for 3.5h; Heating / reflux;	79.6%

3-methylamino-1-thiophen-2-yl-propenone (39145-15-8) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With hydrogen; potassium carbonate; ruthenium(II) chloride In isopropyl alcohol at 30℃; under 18751.9 Torr; for 18h;	79.2%

methylamine (74-89-5) + (S)-1-hydroxy-3-(thiophen-2-yl)propanenitrile (591727-36-5) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With hydrogen; nickel In methanol; water at 65℃; under 37503.8 Torr; for 24h; Product distribution / selectivity;	79%
With hydrogen; 5%-palladium/activated carbon In methanol; water at 60℃; under 75007.5 Torr; for 24h; Product distribution / selectivity;	74%

(S)-3-(N-ethoxycarbonyl-N-methyl)amino-1-ethoxycarbonyloxy-(2-thienyl)propane → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With sodium hydroxide In ethanol; water at 82℃; for 3h;	74.6%

N-methyl-3-(thien-2-yl)-3-morpholino-propylamine hydrochloride → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) + (R)-3-(methylamino)-1-(thiophen-2-yl)propan-1-ol (116539-57-2)

Conditions	Yield
With lithium aluminium tetrahydride Product distribution / selectivity;	A 74% B n/a
With hydrogen; sodium methylate; bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; (S)-(-)-(6,6’-dimethoxybiphenyl-2,2’-diyl)bis(diphenylphosphine) In methanol at 30 - 50℃; under 22502.3 Torr; for 24h; Product distribution / selectivity;	A 12.7 - 20.4 %Chromat. B n/a
With hydrogen; sodium methylate; ethyl acetoacetate; [(12aS)-6,7-dihudrodibenzo[e,g][1,4]dioxocin-1,12-diyl]bis[diphenylphosphine]; bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate In methanol at 50℃; under 22502.3 Torr; for 24h; Product distribution / selectivity;	A 6.2 %Chromat. B n/a
With hydrogen; [(12aS)-6,7-dihudrodibenzo[e,g][1,4]dioxocin-1,12-diyl]bis[diphenylphosphine]; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In methanol at 50℃; under 22502.3 Torr; for 24h; Product distribution / selectivity;	A 11.6 %Chromat. B n/a
With hydrogen; [(12aS)-6,7-dihudrodibenzo[e,g][1,4]dioxocin-1,12-diyl]bis[diphenylphosphine]; bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate In methanol at 50℃; under 22502.3 Torr; for 24h; Product distribution / selectivity;	A 4 %Chromat. B n/a

(S)-3-N-methylammonio-1-(2-thienyl)-1-propanol 2,3:4,6-di-O-isopropylidene-2-keto-L-gulonate → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With potassium hydroxide In water	70%
With sodium carbonate In water for 0.25h;	61%
With sodium hydroxide In water

(S)-N-(3-hydroxy-3-(thiophen-2-yl)propyl)-N-methylacetamide (625853-14-7) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With potassium hydroxide In methanol at 70℃; for 2h;	68%

(S)-MMAA (S)-mandelic acid monohydrate → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With sodium hydroxide In water; iso-butanol	66%

C9H13NO2S → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With bis-[(trifluoroacetoxy)iodo]benzene In water; acetonitrile for 4h; Reflux;	54%

3-N-methylamino-1-(2-thienyl)-1-propanone methanesulphonate → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With formic acid; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; triethylamine; N-[(1S,2S)-2-amino-1,2-diphenylethyl]-4-methylbenzenesulfonamide In methanol at 40 - 45℃; for 2h; Time; Reagent/catalyst;	48%

N-methyl-3-(thien-2-yl)-3-morpholino-propylamine hydrochloride + (1S,2R)-1-amino-2-indanol (7480-35-5, 13286-59-4, 74165-73-4, 126456-43-7, 136030-00-7, 140632-19-5, 140632-20-8) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) + (R)-3-(methylamino)-1-(thiophen-2-yl)propan-1-ol (116539-57-2)

Conditions	Yield
With sodium hydroxide; (p-cymene)-ruthenium(II) chloride dimer In isopropyl alcohol at 20 - 85℃; for 5h;	A 39% B n/a

3-(methylamino)-1-(thiophen-2-yl)propan-1-ol (116539-56-1) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) + (R)-3-(methylamino)-1-(thiophen-2-yl)propan-1-ol (116539-57-2)

Conditions	Yield
With (S)-Mandelic acid In water at 29 - 50℃;	A 27% B n/a
With diethylamine In ethanol; n-heptane Resolution of racemate;

(2S,6S)-2-[(S)-1-triisopropylsilyloxyethyl]-3-methyl-6-(thiophen-2-yl)-1,3-oxazinane (919530-17-9) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 20℃; for 4h;

(2S,6S)-2-[(S)-1-triisopropylsilyloxyethyl]-6-(thiophen-2-yl)-[1,3]oxazinan-4-one (919530-12-4) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: LiHMDS / tetrahydrofuran / 0 - 20 °C 2: Ph2SiH2 / RhH(CO)(PPh3)3 / tetrahydrofuran / 15 h / 20 °C 3: HCl / H2O; tetrahydrofuran / 4 h / 20 °C View Scheme

(2S,6S)-N-methyl-2-[(S)-1-triisopropylsilyloxyethyl]-6-(thiophen-2-yl)-[1,3]oxazinan-4-one (919530-14-6) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Ph2SiH2 / RhH(CO)(PPh3)3 / tetrahydrofuran / 15 h / 20 °C 2: HCl / H2O; tetrahydrofuran / 4 h / 20 °C View Scheme

thiophene-2-carbaldehyde (98-03-3) + polymer-bound-N-(3-(4-bromophenyl)-3-oxopropanamide) → (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 36 percent / BF3*Et2O / CH2Cl2 / -78 - 20 °C 2: aluminum amalgam / propan-2-ol 3: LiHMDS / tetrahydrofuran / 0 - 20 °C 4: Ph2SiH2 / RhH(CO)(PPh3)3 / tetrahydrofuran / 15 h / 20 °C 5: HCl / H2O; tetrahydrofuran / 4 h / 20 °C View Scheme

1-Fluoronaphthalene (321-38-0) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → duloxetine hydrochloride (136434-34-9)

Conditions	Yield
Stage #1: 1-Fluoronaphthalene; (S)-3-methylamino-1-(2-thienyl)-1-propanol With sodium hydride In paraffin oil (nujol); dimethyl sulfoxide at 20 - 50℃; Stage #2: With hydrogenchloride; acetic acid In Isopropyl acetate at 0 - 15℃; for 5h;	93%
Stage #1: (S)-3-methylamino-1-(2-thienyl)-1-propanol With sodium hydride In dimethyl sulfoxide at 20 - 35℃; Stage #2: 1-Fluoronaphthalene In dimethyl sulfoxide at 45 - 50℃; for 30h; Stage #3: With hydrogenchloride In water; dimethyl sulfoxide; toluene pH=4 - 5; Solvent;

1-Fluoronaphthalene (321-38-0) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → Duloxetine (116539-58-3, 116539-59-4, 116539-60-7, 116817-13-1)

Conditions	Yield
With potassium tert-butylate In dimethyl sulfoxide at 60℃; for 8h;	90%
With potassium tert-butylate In dimethyl sulfoxide at 60℃; for 8h;	90%
With sodium hydride In dimethyl sulfoxide for 8h;	81%

benzenesulfonyl chloride (98-09-9) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → N-[3S-hydroxy-3-(thiophen-2-yl)propyl]-N-methylbenzenesulfonamide

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 14h;	90%

3-fluorobromobenzene (1073-06-9) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → (S)-3-(3-bromophenoxy)-N-methyl-3-(thiophen-2-yl)propan-1-amine

Conditions	Yield
Stage #1: (S)-3-methylamino-1-(2-thienyl)-1-propanol With sodium hydride In N,N-dimethyl acetamide; mineral oil at 20℃; for 0.5h; Stage #2: 3-fluorobromobenzene In N,N-dimethyl acetamide; mineral oil at 90℃; for 3h;	90%
Stage #1: (S)-3-methylamino-1-(2-thienyl)-1-propanol With sodium hydride In N,N-dimethyl acetamide; mineral oil at 20℃; for 0.5h; Stage #2: 3-fluorobromobenzene In N,N-dimethyl acetamide; mineral oil at 90℃; for 3h;

(1S)-10-camphorsulfonic acid (3144-16-9) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → (S)-3-methylamino-1-thiophen-2-yl-propan-1-ol 1-(S)-(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)-methanesulfonate

Conditions	Yield
In ethanol; ethyl acetate at 30 - 50℃; for 0.916667h; Product distribution / selectivity;	89%

toluene-4-sulfonic acid (104-15-4) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → (S)-(-)-3-N-methylamino-1-(2-thienyl)-1-propanol p-toluenesulfonate

Conditions	Yield
In methanol; dichloromethane at 25℃; for 1h; Product distribution / selectivity;	60%

4-[2-(tert-butyldimethylsilyloxy)ethyl]phenol (96013-76-2) + (S)-3-methylamino-1-(2-thienyl)-1-propanol (116539-55-0) → (R)-3-[4-[2-(tert-butyldimethylsilyloxy)ethyl]phenoxy]-N-methyl-3-(thiophen-2-yl)propan-1-amine (1615654-56-2)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In ethyl acetate; toluene	52%
With triphenylphosphine; diethylazodicarboxylate In toluene at 20℃; for 18h;	52%

Upstream product

• 74-89-5 methylamine 
• 591727-36-5 (S)-3-hydroxy-3-(thiophen-2-yl)propanenitrile 
• 98-03-3 thiophene-2-carbaldehyde 
• 1374030-94-0 (S)-3-(diallylamino)-1-(thiophen-2-yl)propan-1-ol 
• 39145-15-8 (E)-N-methyl-3-(thiophen-2-yl)-acrylamide 
• 87702-21-4 4-(thien-2-yl)-4-oxobutyric acid methyl ester 
• 4653-08-1 4-oxo-4-thiophen-2-yl-butyric acid 
• 625853-22-7 phenyl (S)-N-[3-acetoxy-3-(thien-2-yl)propyl]-N-methylcarbamate 
• 164071-56-1 (S)-3-chloro-1-(thiophen-2-yl)propan-1-ol 
• 645411-16-1 N-methyl-3-(thien-2-yl)-3-morpholino-propylamine hydrochloride 
• 124-40-3 dimethyl amine 
• 164071-58-3 S-(-)-3-iodo-1-(2-thienyl)-1-propanol 
• 89639-64-5 (E)-3-(thien-2-yl)prop-2-en-1-ol 
• 1124-65-8 3-(2-thienyl)-2-propenoic acid 

Downstream Products

• 116817-77-7 Duloxetine oxalate 
• 116539-60-7 (R)-Duloxetine 
• 1615654-19-7 (R)-2-[4-[3-(Methylamino)-1-(thiophen-2-yl)propoxy]phenyl]ethanol 
• 1615654-56-2 (R)-3-[4-[2-(tert-butyldimethylsilyloxy)ethyl]phenoxy]-N-methyl-3-(thiophen-2-yl)propan-1-amine 
• 136434-34-9 duloxetine hydrochloride 
• 116817-13-1 duloxetine 
• 116539-58-3 Duloxetine 
• 132335-44-5 (S)-3-dimethylamino-1-(2-thienyl)propan-1-ol 

Relevant articles and documents

An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers

Two 14C-isotopomers of duloxetine HCl (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride), a potent mixed serotonin/norepinephrine Uptake inhibitor have been prepared by an asymmetric synthesis. The palladium catalyzed cross-coupling of 2-thienoyl chloride (3c) (or its [carbonyl-14C] isotopomer 3d) with vinyl tri-n-butylstannane, followed by addition of HCl afforded the key pro-chiral intermediate chloroketone (5a,b). Chiral reduction with borane in the presence of the appropriate oxazaborolidine catalyst (14a or b) provided the S-chloroalcohol (7a) and its 14C-labeled counterpart 7b or the analogous R-chloroalcohol (6). Activation of 7a,b by reaction with NaI/acetone, followed by reaction of the corresponding iodoalcohol with methylamine yielded the penultimate aminoalcohols (8a,b). Formation of the alkoxide with NaH, followed by reaction with 1-fluoronaphthalene yielded duloxetine or its 14C-labeled isotopomer 9. Alternatively, reaction of 6 with 1-naphthol-[1-14C] under Mitsunobu conditions afforded aryl-ether 10a,b, which was in turn activated by reaction with NaI/acetone Subsequent reaction of 10c,d with methylamine followed by salt formation yielded duloxetine or its naphthalene-labeled isotopomer (13) as their HCl salts.

Resolution of 3-(methylamino)-1-(2-thienyl)propan-1-ol, a new key intermediate for duloxetine, with (S)-mandelic acid

The resolution of racemic 3-(methylamino)-1-(2-thienyl)propan-1-ol 3, a new key intermediate for duloxetine 1, was studied. The conditions were optimized for an industrial-scale resolution of 3 by using (S)-mandelic acid 4 as a resolving agent and 2-butanol containing 2 equimolar amounts of water as a solvent. The (S)-3·(S)-4·H2O diastereomeric salt was crystallized to give pure (S)-3 with >99.9% e.e. after liberation of the amine. The absolute configuration of liberated (-)-3 was determined as (S) by X-ray crystallography.

Method for synthesizing (S)-3-methylamino-1-(thiophene-2-yl) propyl alcohol

The invention discloses a method for synthesizing (S)-3-methylamino-1-(thiophene-2-yl) propyl alcohol. The method is characterized by comprising the following steps: taking 3-methylamino-1-(thiophene-2-yl) acetone as a raw material in an environment of alkali and solvents, carrying out a catalytic hydrogenation reaction in the presence of a transition metal complex catalyst, thereby obtaining the(S)-3-methylamino-1-(thiophene-2-yl) propyl alcohol. According to the method disclosed by the invention, the high-purity product can be obtained by the one-step catalytic hydrogenation reaction only,the process cycle is greatly shortened, the catalyst amount is small, the production cost is low, the reaction conditions are mild, the process is stable, the conversion rate is high, the environmental pollution produced in the reaction is less, and industrialized production is facilitated.

west Luo river sandbank chiral method for the preparation of intermediates

The invention relates to a preparation method of a chiral duloxetine intermediate, namely (S)-N-methyl-3-hydroxy-(2-thienyl)-1-propylamine, belonging to the technical field of drug synthesis. The preparation method comprises the following steps: reacting trans-N-methyl-3-(2-thienyl)-crotonamide with a boron compound in a solvent in the presence of a chiral catalyst, copper salt and alkali under the nitrogen protection to obtain a reaction product, and performing oxidation reduction on the reaction product to obtain (S)-N-methyl-3-hydroxy-(2-thienyl)-1-propylamine. The preparation method is easy and feasible; the prepared target product is high in yield and optical purity, low in purification difficulty and suitable for a research on scale production.