30356-07-1

Basic information

• Product Name: (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline
• Synonyms: (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline;1-(4-METHOXY-BENZYL)-1,2,3,4,5,6,7,8-OCTAHYDRO-ISOQUINOLINE;Einecs 250-144-5;(S)-1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline;Isoquinoline,1,2,3,4,5,6,7,8-octahydro-1-[(4-Methoxyphenyl)Methyl]-, (1S)-
• CAS NO: 30356-07-1
• Molecular Formula: C₁₇H₂₃NO
• Molecular Weight: 257.37062
• EINECS: 250-144-5
• Product Categories: CMLLYL
• Mol File: 30356-07-1.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 394.8°Cat760mmHg
• Flash Point: 165.6°C
• Appearance: /
• Density: 1.07g/cm³
• Vapor Pressure: 1.93E-06mmHg at 25°C
• Refractive Index: 1.567
• PKA: 10.20±0.40(Predicted)
• CAS DataBase Reference: (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline(30356-07-1)
• EPA Substance Registry System: (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline(30356-07-1)

Safety Data

• Hazardous Substances Data: 30356-07-1(Hazardous Substances Data)

Usage

General Description

"(S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline" is a synthetic compound that belongs to the chemical class known as isoquinolines. The complex name indicates it's a stereochemically specific version (S isomer) of an isoquinoline derivative. It features an octahydroisoquinoline backbone substituted at the first position by a (4-methoxyphenyl)methyl group. The isoquinoline skeleton plays a significant role in medicinal chemistry due to its wide applications in pharmaceuticals, while methoxyphenyl is a common moiety involved in the structure of bioactive molecules. The exact properties, safety profile and uses of this molecule would have to be determined experimentally or through detailed literature study, but it could potentially be a precursor or an active part in the synthesis of biologically relevant molecules.

InChI:InChI=1/C17H23NO/c1-19-15-8-6-13(7-9-15)12-17-16-5-3-2-4-14(16)10-11-18-17/h6-9,17-18H,2-5,10-12H2,1H3/t17-/m0/s1

Synthetic route

((S)-1-tert-Butoxymethyl-2-methyl-propyl)-[1-[(S)-1-(4-methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-meth-(E)-ylidene]-amine (100466-49-7) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With acetic acid; hydrazine In ethanol at 50℃; for 12h;	81%

C26H40N2O2 → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With acetic acid; hydrazine In ethanol at 50℃; for 12h; Inert atmosphere;	81%
With acetic acid; hydrazine In ethanol at 50℃; for 12h; Inert atmosphere;	81%

(+)-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (51072-36-7) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With ammonia borane; oxygen In aq. phosphate buffer at 35℃; under 760.051 Torr; for 72h; pH=7.5; Reagent/catalyst; Enzymatic reaction; stereoselective reaction;	80%
With (S)-Mandelic acid In water; toluene at 75 - 80℃; for 1h;

1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinoline hydrochloride → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With D-glucose; NADP In dimethyl sulfoxide at 25℃; for 18h; pH=9; Kinetics; Reagent/catalyst; Temperature; pH-value; Solvent; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	74%

(+/-)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline hydrobromide (93477-35-1) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Stage #1: (+/-)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline hydrobromide With sodium hydroxide In water; toluene Stage #2: With acetic acid In toluene at 20℃; for 0.166667h; Stage #3: With (S)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline acetate In toluene at 10℃; for 2h; Temperature;	30.3%

2-Formyl-1-<(4-methoxyphenyl)methyl>-1,2,3,4,5,6,7,8-octahydroispquinoline (63477-91-8) → (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline (30356-08-2) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With sodium hydroxide In ethanol at 80℃; for 10h; Yields of byproduct given. Title compound not separated from byproducts;

4-((S)-1,2,3,4,5,6,7,8-octahydro-[1]isoquinolylmethyl)-phenol (74570-02-8, 94006-09-4, 109866-75-3, 125158-41-0) + reagent from trimethyl-phenyl-ammonium chloride and KOH-solution → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With methanol; toluene

1,2,3,4,5,6,7,8-octahydroisoquinoline (2721-62-2) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene / 48 h / 85 °C 2: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 3: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: Cu2O / toluene / 16 h / Heating 2: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 3: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: copper(I) oxide / toluene / 16 h / Reflux 2: n-butyllithium / tetrahydrofuran; hexane / 2 h / -78 - 0 °C / Inert atmosphere 3: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: copper(I) oxide / toluene / 16 h / Reflux 2: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 - 0 °C / Inert atmosphere 3: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

3,4,5,6,7,8-Hexahydro-1H-isoquinoline-2-carboxylic acid methyl ester → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 2: toluene / 48 h / 85 °C 3: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 4: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 2: Cu2O / toluene / 16 h / Heating 3: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 4: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme

3,4,5,6,7,8-Hexahydro-1H-isoquinoline-2-carboxylic acid phenyl ester → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 2: toluene / 48 h / 85 °C 3: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 4: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 2: Cu2O / toluene / 16 h / Heating 3: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 4: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme

((S)-1-tert-Butoxymethyl-2-methyl-propyl)-[1-(3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl)-meth-(E)-ylidene]-amine (100466-48-6) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 2: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme

N-benzyl-5,6,7,8-tetrahydroisoquinolinium bromide (100466-46-4) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 93 percent / NaBH4 / methanol; H2O / 1 h / Heating 2: CH2Cl2 / 2 h 3: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 4: toluene / 48 h / 85 °C 5: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 6: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 6 steps 1: 93 percent / NaBH4 / methanol; H2O / 1 h / Heating 2: CH2Cl2 / 2 h 3: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 4: Cu2O / toluene / 16 h / Heating 5: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 6: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 6 steps 1: 93 percent / NaBH4 / methanol; H2O / 1 h / Heating 2: CH2Cl2 / 2 h 3: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 4: toluene / 48 h / 85 °C 5: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 6: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 6 steps 1: 93 percent / NaBH4 / methanol; H2O / 1 h / Heating 2: CH2Cl2 / 2 h 3: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 4: Cu2O / toluene / 16 h / Heating 5: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 6: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1: sodium tetrahydroborate / methanol; water / 2 h / 0 °C / Reflux 2: methyl chloroformate / dichloromethane / 2 h / 0 - 20 °C 3: copper(I) oxide / toluene / 16 h / Reflux 4: n-butyllithium / tetrahydrofuran; hexane / 2 h / -78 - 0 °C / Inert atmosphere 5: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

N-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline (100466-47-5) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: CH2Cl2 / 2 h 2: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 3: toluene / 48 h / 85 °C 4: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 5: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1: CH2Cl2 / 2 h 2: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 3: Cu2O / toluene / 16 h / Heating 4: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 5: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1: CH2Cl2 / 2 h 2: 18-crown-6, KOH / tetrahydrofuran / 48 h / Heating 3: toluene / 48 h / 85 °C 4: 66 percent / n-BuLi / tetrahydrofuran; hexane / -78 - 0 °C 5: 81 percent / hydrazine, AcOH / aq. ethanol / 12 h / 50 °C View Scheme

C18H32N2O → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: n-butyllithium / tetrahydrofuran; hexane / 2 h / -78 - 0 °C / Inert atmosphere 2: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 - 0 °C / Inert atmosphere 2: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

isoquinoline (119-65-3) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: trifluoroacetic acid; 5%-palladium/activated carbon; hydrogen / 48 h / 50 °C / 2585.81 Torr 2: acetone / 1 h / Reflux 3: sodium tetrahydroborate / methanol; water / 2 h / 0 °C / Reflux 4: methyl chloroformate / dichloromethane / 2 h / 0 - 20 °C 5: copper(I) oxide / toluene / 16 h / Reflux 6: n-butyllithium / tetrahydrofuran; hexane / 2 h / -78 - 0 °C / Inert atmosphere 7: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: trifluoroacetic acid; 5%-palladium/activated carbon; hydrogen / 48 h / 50 °C / 2585.81 Torr 2.1: acetone / 1 h / Reflux 3.1: sodium tetrahydroborate / water; ethanol / 1 h / 0 °C / Reflux 4.1: methyl chloroformate / dichloromethane / 2 h / 0 - 20 °C 4.2: 48 h / Inert atmosphere; Reflux 5.1: copper(I) oxide / toluene / 16 h / Reflux 6.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 - 0 °C / Inert atmosphere 7.1: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

5,6,7,8-tetrahydroisoquinoline (36556-06-6) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: acetone / 1 h / Reflux 2: sodium tetrahydroborate / methanol; water / 2 h / 0 °C / Reflux 3: methyl chloroformate / dichloromethane / 2 h / 0 - 20 °C 4: copper(I) oxide / toluene / 16 h / Reflux 5: n-butyllithium / tetrahydrofuran; hexane / 2 h / -78 - 0 °C / Inert atmosphere 6: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

5,6,7,8-tetrahydroisoquinoline → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: acetone / 1 h / Reflux 2.1: sodium tetrahydroborate / water; ethanol / 1 h / 0 °C / Reflux 3.1: methyl chloroformate / dichloromethane / 2 h / 0 - 20 °C 3.2: 48 h / Inert atmosphere; Reflux 4.1: copper(I) oxide / toluene / 16 h / Reflux 5.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 - 0 °C / Inert atmosphere 6.1: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

C16H20N(1+)*Br(1-) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sodium tetrahydroborate / water; ethanol / 1 h / 0 °C / Reflux 2.1: methyl chloroformate / dichloromethane / 2 h / 0 - 20 °C 2.2: 48 h / Inert atmosphere; Reflux 3.1: copper(I) oxide / toluene / 16 h / Reflux 4.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 - 0 °C / Inert atmosphere 5.1: hydrazine; acetic acid / ethanol / 12 h / 50 °C / Inert atmosphere View Scheme

4-Methoxyphenylacetic acid (104-01-8) + 2-(1-cyclohexenyl)ethylamine (3399-73-3) → (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline (30356-08-2) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Stage #1: 4-Methoxyphenylacetic acid; 2-(1-cyclohexenyl)ethylamine In 5,5-dimethyl-1,3-cyclohexadiene at 70 - 80℃; Dean-Stark; Stage #2: With trichlorophosphate In 5,5-dimethyl-1,3-cyclohexadiene at 50 - 110℃; for 3.16667h; Stage #3: With (S)-Mandelic acid

2-(1-cyclohexenyl)ethylamine (3399-73-3) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 5,5-dimethyl-1,3-cyclohexadiene / 70 - 80 °C / Dean-Stark 1.2: 3.17 h / 50 - 110 °C 1.3: 25 - 30 °C / pH 5 - 5.5 2.1: (S)-Mandelic acid / toluene; water / 1 h / 75 - 80 °C View Scheme
Multi-step reaction with 3 steps 1.1: 5,5-dimethyl-1,3-cyclohexadiene / 70 - 80 °C / Dean-Stark 1.2: 3.17 h / 50 - 110 °C 2.1: sodium hypochlorite / tert-butyl methyl ether / 4 h / -10 - 25 °C 2.2: 2 h / 5 - 25 °C 2.3: 2 h / 5 - 25 °C 3.1: (S)-Mandelic acid / toluene; water / 1 h / 75 - 80 °C View Scheme
Multi-step reaction with 4 steps 1.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 °C / Inert atmosphere 2.1: trichlorophosphate / toluene / 4 h / 85 - 105 °C 2.2: 20 °C 3.1: sodium tetrahydroborate / methanol / 4 h / 20 °C 4.1: ammonia borane; oxygen / aq. phosphate buffer / 72 h / 35 °C / 760.05 Torr / pH 7.5 / Enzymatic reaction View Scheme

(R)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline L-mandelate → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / 0.5 h / 25 - 30 °C / pH 12 - 13.5 2.1: sodium hypochlorite / tert-butyl methyl ether / 4 h / -10 - 25 °C 2.2: 2 h / 5 - 25 °C 2.3: 2 h / 5 - 25 °C 3.1: (S)-Mandelic acid / toluene; water / 1 h / 75 - 80 °C View Scheme

(S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline (30356-08-2) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hypochlorite / tert-butyl methyl ether / 4 h / -10 - 25 °C 1.2: 2 h / 5 - 25 °C 1.3: 2 h / 5 - 25 °C 2.1: (S)-Mandelic acid / toluene; water / 1 h / 75 - 80 °C View Scheme

1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydro-isoquinoline (51072-35-6) → (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline (30356-08-2) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With (R)-N-(5-fluoro-2-hydroxybenzyl)-2-methylpropane-2-sulfinamide; trichlorosilane In dichloromethane at -20 - -15℃; for 12.5h; Inert atmosphere;	A n/a B n/a

1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinoline hydrochloride → (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline (30356-08-2) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
With D-glucose; NADP In aq. phosphate buffer; dimethyl sulfoxide at 30℃; for 18h; pH=7.5; Kinetics; Reagent/catalyst; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a
With D-glucose; NADP In aq. phosphate buffer; dimethyl sulfoxide at 30℃; for 18h; pH=7.5; Kinetics; Reagent/catalyst; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

N-(2-cyclohex-1-enylethyl)-2-(4-methoxyphenyl)-acetamide (51072-34-5) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate / toluene / 8 h / Reflux 2: D-glucose; NADP / dimethyl sulfoxide / 18 h / 25 °C / pH 9 / Inert atmosphere; Enzymatic reaction View Scheme
Multi-step reaction with 3 steps 1.1: trichlorophosphate / toluene / 4 h / 85 - 105 °C 1.2: 20 °C 2.1: sodium tetrahydroborate / methanol / 4 h / 20 °C 3.1: ammonia borane; oxygen / aq. phosphate buffer / 72 h / 35 °C / 760.05 Torr / pH 7.5 / Enzymatic reaction View Scheme

4-Methoxyphenylacetic acid (104-01-8) → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 °C / Inert atmosphere 2.1: trichlorophosphate / toluene / 4 h / 85 - 105 °C 2.2: 20 °C 3.1: sodium tetrahydroborate / methanol / 4 h / 20 °C 4.1: ammonia borane; oxygen / aq. phosphate buffer / 72 h / 35 °C / 760.05 Torr / pH 7.5 / Enzymatic reaction View Scheme

1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydro-isoquinoline hydrogen sulphate → (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 4 h / 20 °C 2: ammonia borane; oxygen / aq. phosphate buffer / 72 h / 35 °C / 760.05 Torr / pH 7.5 / Enzymatic reaction View Scheme

di-tert-butyl dicarbonate (24424-99-5) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (S)-1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Conditions	Yield
With triethylamine In dichloromethane at 0 - 30℃; for 2h;	99%

formic acid (64-18-6) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (S)-2-Formyl-1-<(4-methoxyphenyl)methyl>-1,2,3,4,5,6,7,8-octahydroispquinoline (29144-31-8)

Conditions	Yield
In toluene Reflux;	95%

naphthalene-1-carbonic acid chloride (879-18-5) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → [(S)-1-(4-Methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-naphthalen-1-yl-methanone (90133-19-0)

Conditions	Yield
With triethylamine In dichloromethane Ambient temperature;

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) + formic acid ethyl ester (109-94-4) → (S)-2-Formyl-1-<(4-methoxyphenyl)methyl>-1,2,3,4,5,6,7,8-octahydroispquinoline (29144-31-8)

Conditions	Yield
at 40℃; for 15h;
at 40℃; for 15h;

formaldehyd (50-00-0) + toluene-4-sulfonic acid (104-15-4) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → Toluene-4-sulfonate(S)-1-(4-methoxy-benzyl)-2-methylene-1,2,3,4,5,6,7,8-octahydro-isoquinolinium;

Conditions	Yield
In dichloromethane for 3h;

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → O-{4-[(1R)-(4-methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-(1S)-methyl-but-2-ynyl}-hydroxylamine

Conditions	Yield
Multi-step reaction with 2 steps 1.1: CH2Cl2 / 3 h 2.1: polystyrene-bound N-hydroxyphthalimide resin; azodicarboxylic acid bis[dimethylamide]; P(n-Bu)3 / CH2Cl2; tetrahydrofuran / 6 h / 20 °C 2.2: CuBr / dimethylformamide / 12 h / 50 °C 2.3: 95 percent / NH2NH2 / CH2Cl2 / 1 h View Scheme

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (Z)-(3S)-7-dimethyl-oct-6-enal O-{4-[(1R)-(4-methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-(1S)-methyl-but-2-ynyl}-oxime

Conditions	Yield
Multi-step reaction with 3 steps 1.1: CH2Cl2 / 3 h 2.1: polystyrene-bound N-hydroxyphthalimide resin; azodicarboxylic acid bis[dimethylamide]; P(n-Bu)3 / CH2Cl2; tetrahydrofuran / 6 h / 20 °C 2.2: CuBr / dimethylformamide / 12 h / 50 °C 2.3: 95 percent / NH2NH2 / CH2Cl2 / 1 h 3.1: 1,2-dichloro-ethane / 0.25 h / 120 °C / microwave irradiation 3.2: PL-MIA resin / CH2Cl2 / 4 h / 20 °C View Scheme

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (E)-(3S)-7-dimethyl-oct-6-enal O-{4-[(1R)-(4-methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-(1S)-methyl-but-2-ynyl}-oxime

Conditions	Yield
Multi-step reaction with 3 steps 1.1: CH2Cl2 / 3 h 2.1: polystyrene-bound N-hydroxyphthalimide resin; azodicarboxylic acid bis[dimethylamide]; P(n-Bu)3 / CH2Cl2; tetrahydrofuran / 6 h / 20 °C 2.2: CuBr / dimethylformamide / 12 h / 50 °C 2.3: 95 percent / NH2NH2 / CH2Cl2 / 1 h 3.1: 1,2-dichloro-ethane / 0.25 h / 120 °C / microwave irradiation 3.2: PL-MIA resin / CH2Cl2 / 4 h / 20 °C View Scheme

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (+)-dextrorphan (125-73-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 15 h / 40 °C 2: LiAlH4 / diethyl ether / 2 h / Ambient temperature 3: 45 percent / H3PO4 / 65 h / 135 - 140 °C View Scheme

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (S)-(+)-N-methyl-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (89614-56-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 15 h / 40 °C 2: LiAlH4 / diethyl ether / 2 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: toluene / Reflux 2: potassium borohydride / water; methanol / 1 h View Scheme

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → dextrorphan

Conditions	Yield
Multi-step reaction with 3 steps 1: 15 h / 40 °C 2: lithium aluminium tetrahydride / diethyl ether / 2 h / 20 °C 3: phosphoric acid / 65 h / 135 - 140 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: 15 h / 40 °C 2: lithium aluminium tetrahydride / diethyl ether / 2 h / 20 °C 3: phosphoric acid / 65 h / 135 - 140 °C / Inert atmosphere View Scheme

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → C37H51NO2

Conditions	Yield
Multi-step reaction with 4 steps 1: 15 h / 40 °C 2: lithium aluminium tetrahydride / diethyl ether / 2 h / 20 °C 3: phosphoric acid / 65 h / 135 - 140 °C / Inert atmosphere 4: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 24 h / 20 °C View Scheme

phenylacetyl chloride (103-80-0) + (1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → (+)-N-phenylacetyl octabase

Conditions	Yield
With sodium hydroxide for 0.166667h;

(1S)-1-[(4-methoxyphenyl)methyl]-1,2,3,4,5,6,7,8-octahydroisoquinoline (30356-07-1) → C37H51NO2

Conditions	Yield
Multi-step reaction with 4 steps 1: 15 h / 40 °C 2: lithium aluminium tetrahydride / diethyl ether / 2 h / 20 °C 3: phosphoric acid / 65 h / 135 - 140 °C / Inert atmosphere 4: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 2 h / 20 °C View Scheme

Upstream product

• 63477-91-8 2-Formyl-1-<(4-methoxyphenyl)methyl>-1,2,3,4,5,6,7,8-octahydroispquinoline 
• 100466-49-7 ((S)-1-tert-Butoxymethyl-2-methyl-propyl)-[1-[(S)-1-(4-methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-meth-(E)-ylidene]-amine 
• 74570-02-8 4-((S)-1,2,3,4,5,6,7,8-octahydro-[1]isoquinolylmethyl)-phenol 
• 2721-62-2 1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 100466-48-6 ((S)-1-tert-Butoxymethyl-2-methyl-propyl)-[1-(3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl)-meth-(E)-ylidene]-amine 
• 100466-46-4 N-benzyl-5,6,7,8-tetrahydroisoquinolinium bromide 
• 100466-47-5 N-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 119-65-3 isoquinoline 
• 36556-06-6 5,6,7,8-tetrahydroisoquinoline 
• 51072-36-7 (+)-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 104-01-8 4-Methoxyphenylacetic acid 
• 3399-73-3 2-(1-cyclohexenyl)ethylamine 
• 94992-57-1 (R)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline L-mandelate 
• 30356-08-2 (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline 

Downstream Products

• 90133-19-0 [(S)-1-(4-Methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-naphthalen-1-yl-methanone 
• 29144-31-8 (S)-2-Formyl-1-<(4-methoxyphenyl)methyl>-1,2,3,4,5,6,7,8-octahydroispquinoline 
• 125-73-5 (+)-dextrorphan 
• 89614-56-2 (S)-(+)-N-methyl-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 94006-07-2 (S)-(+)-N-formyl-1-(p-hydroxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 74570-02-8 4-((S)-1,2,3,4,5,6,7,8-octahydro-[1]isoquinolylmethyl)-phenol 

Relevant articles and documents

Imine Reductase-Catalyzed Enantioselective Reduction of Bulky α,β-Unsaturated Imines en Route to a Pharmaceutically Important Morphinan Skeleton

The morphinan skeleton is an important sub-structure in many medicines such as dextromethorphan, and can be constructed from 1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline (1-benzyl-OHIQ) derivatives. 1-Benzyl-3,4,5,6,7,8-hexahydroisoquinolines (1-benzyl-HHIQs), the precursors of 1-benzyl-OHIQs, constitute a type of bulky α, β-unsaturated imines. Until now, the application of imine reductases (IREDs) to α, β-unsaturated imines has only rarely been reported. In this study, through evaluation of 48 IREDs, both enantiomers of 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (1-(4-methoxybenzyl)-OHIQ) were obtained in high yield and excellent optical purity. Among the enzymes, the most steric hindrance-tolerant IRED from Sandarearacinus amylolyticus (IR40) was able to convert various phenyl substituted 1-benzyl-HHIQ to the corresponding 1-benzyl-OHIQ derivatives with excellent enantiometric excess. These results provide an effective route to synthesize these important compounds via enantioselective reduction of bulky α, β-unsaturated imine precursors, which can be readily prepared from 2-(1-cyclohexenyl)ethylamine and corresponding aryl acetic acids. (Figure presented.).

A (S) or (R)- 1 - (4 - methoxybenzyl) - 1, 2, 3, 4, 5, 6, 7, 8 - quinoline of eight hydrogens different preparation method

The invention discloses a preparation method of (S) or (R)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate, wherein the method includes the steps: (1) mixing an aromatic solution of a compound having a structure represented by the formula III with acetic acid, to obtain a solution 1; (2) adding a (S)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate seed crystal or a (R)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate seed crystal into the solution 1, to obtain a solution 2; and (3) cooling the solution 2 to 0-5 DEG C, crystallizing to obtain (S)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate or (R)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate.

AN IMPROVED PROCESS FOR THE PREPARATION OF BUTORPHANOL TARTRATE

The present invention relates to an improved process for the preparation of Butorphanol tartrate of formula (I),