4684-28-0

Basic information

• Product Name: [7(S)-(1alpha,.2beta,4beta,5alpha,7beta)]-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (hydroxymethyl)phenylacetate
• Synonyms: [7(S)-(1alpha,.2beta,4beta,5alpha,7beta)]-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (hydroxymethyl)phenylacetate;Norscopolamin;(S)-α-(Hydroxymethyl)benzeneacetic acid (1α,2β,4β,5α)-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7β-yl ester;(7(S)-(1alpha,2beta,4beta,5alpha,7beta))-3-Oxa-9-azatricyclo(3.3.1.02,4)non-7-yl (hydroxymethyl)phenylacetate;Benzeneacetic acid, alpha-(hydroxymethyl)-, 3-oxa-9-azatricyclo(3.3.1.0(2,4))non-7-yl ester, (7(S)-(1alpha,2beta,4beta,5alpha,7beta))-;Einecs 225-139-6;Norhyoscine;[7(S)-(1α,2β,4β,5α,7β)]-α-(HydroxyMethyl)-benzeneacetic Acid 3-Oxa-9-azatricyclo[3.3.1.02,4]non-7-yl Ester
• CAS NO: 4684-28-0
• Molecular Formula: C₁₆H₁₉NO₄
• Molecular Weight: 289.32636
• EINECS: 225-139-6
• Mol File: 4684-28-0.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 474.7°Cat760mmHg
• Flash Point: 240.9°C
• Appearance: /
• Density: 1.34g/cm³
• PKA: 14.11±0.10(Predicted)
• CAS DataBase Reference: [7(S)-(1alpha,.2beta,4beta,5alpha,7beta)]-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (hydroxymethyl)phenylacetate(CAS DataBase Reference)
• NIST Chemistry Reference: [7(S)-(1alpha,.2beta,4beta,5alpha,7beta)]-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (hydroxymethyl)phenylacetate(4684-28-0)
• EPA Substance Registry System: [7(S)-(1alpha,.2beta,4beta,5alpha,7beta)]-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (hydroxymethyl)phenylacetate(4684-28-0)

Safety Data

• RIDADR: UN 1544PSN1 6.1 / PGI
• Hazardous Substances Data: 4684-28-0(Hazardous Substances Data)

Usage

Chemical Properties

Off-white Solid

Uses

Scopolamine (S200000) metabolite.

Synthetic route

scopolamine (51-34-3, 138-12-5, 64069-63-2, 124917-17-5) → Norscopolamine (4684-28-0)

Conditions	Yield
With sodium perchlorate; water for 3h; Electrochemical reaction; Green chemistry;	83%
Stage #1: scopolamine With 1,4-diaza-bicyclo[2.2.2]octane; tri(4-tolyl)aminium hexafluorophosphate In acetonitrile at -5℃; Inert atmosphere; Stage #2: In tetrahydrofuran; acetonitrile at 0℃; Inert atmosphere; regioselective reaction;	36%

hyoscine hydrobromide (114-49-8) → Norscopolamine (4684-28-0)

Conditions	Yield
With potassium permanganate; potassium carbonate
(i) Ac2O, (ii) aq. Na2CO3, KMnO4, (iii) aq. HCl; Multistep reaction;
With potassium permanganate; sulfuric acid; sodium carbonate In water at 30℃; for 2h; (pH=7); Yield given;

(S)-3-acetoxy-2-phenyl-propionic acid (1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester (5027-68-9) → Norscopolamine (4684-28-0)

Conditions	Yield
With hydrogenchloride for 1h; Heating;

(-)-N-Chlorformyl-O-acetylnorscopolamin (25645-57-2) → Norscopolamine (4684-28-0)

Conditions	Yield
(i) H2O, (ii) aq. HCl; Multistep reaction;
Multi-step reaction with 2 steps 1: H2O / 1 h / 93 °C 2: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C View Scheme
Multi-step reaction with 3 steps 1: H2O / 1 h / 93 °C 2: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C 3: 20percent HCl View Scheme

(S)-3-hydroxy-2-phenyl-propionic acid 9-formyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester; hydrochloride (25650-60-6) → Norscopolamine (4684-28-0)

Conditions	Yield
With hydrogenchloride at 75℃; for 0.5h;

(-)-Formylnorscopollamin (25650-58-2) → Norscopolamine (4684-28-0)

Conditions	Yield
With hydrogenchloride

(-)-O-Acetylnorscopolamin-hydrochlorid → Norscopolamine (4684-28-0) + (-)-Formylnorscopollamin (25650-58-2)

Conditions	Yield
With hydrogenchloride; sodium hydroxide 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C;

(-)-O-Acetylnorscopolamin-hydrochlorid → Norscopolamine (4684-28-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C 2: 20percent HCl View Scheme

9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]non-7-yl-3'-(acetyloxy)-2'-phenyl propanoate (6820-79-7) → Norscopolamine (4684-28-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT 2: H2O / 1 h / 93 °C 3: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C View Scheme
Multi-step reaction with 4 steps 1: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT 2: H2O / 1 h / 93 °C 3: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C 4: 20percent HCl View Scheme
Multi-step reaction with 2 steps 1: COCl2 / CH2Cl2 2: (i) H2O, (ii) aq. HCl View Scheme

C19H22ClNO6 → Norscopolamine (4684-28-0)

Conditions	Yield
In methanol for 2h; Heating;	0.20 g

1,4-dibromo-butane (110-52-1) + Norscopolamine (4684-28-0) → (-)-Azoniaspiro-(norscopolamin-8,1'-pyrrolidin)-bromid (26352-27-2)

Conditions	Yield
In acetonitrile at 80℃; for 25h;	80.1%
In ethanol at 110℃; for 30h;

oxirane (75-21-8) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-(2-hydroxy-ethyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

ethyloxirane (106-88-7) + Norscopolamine (4684-28-0) → (S)-2-phenyl-acrylic acid 9-(2-hydroxy-butyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

ethyloxirane (106-88-7) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-((Ξ)-2-hydroxy-butyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

1-oxaspiro(2.5)octane (185-70-6) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-((1Ξ)-ξ-2-hydroxy-cyclohexylmethyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

1,4-dibromo-butane (110-52-1) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9,9'-butane-1,4-diyl-bis-((1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl) ester

Conditions	Yield
In ethanol at 110℃; for 30h;

Propyl isocyanate (110-78-1) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-propylcarbamoyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester (26352-40-9)

Conditions	Yield
In acetone at 5℃; for 10h;

benzyl methyl ether (538-86-3) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-((Ξ)-2-hydroxy-2-phenyl-ethyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

1,5-dibromo-pentane (111-24-0) + Norscopolamine (4684-28-0) → 7t-((S)-3-hydroxy-2-phenyl-propionyloxy)-(1rN,2tH,4tH,5cN)-spiro[3-oxa-9-aza-tricyclo[3.3.1.02,4]nonanium-9,1'-piperidinium]; bromide (26352-28-3)

Conditions	Yield
In ethanol at 110℃; for 30h;

1-iodo-butane (542-69-8) + Norscopolamine (4684-28-0) → N-butylscopolamine (14861-14-4)

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

1-Iodoheptane (4282-40-0) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-heptyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester (36435-52-6)

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

amyl iodide (628-17-1) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-pentyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

1,5-dichloropentane (628-76-2) + Norscopolamine (4684-28-0) → 7t-((S)-3-hydroxy-2-phenyl-propionyloxy)-(1rN,2tH,4tH,5cN)-spiro[3-oxa-9-aza-tricyclo[3.3.1.02,4]nonanium-9,1'-piperidinium]; perchlorate

Conditions	Yield
(i) Et3N, MeCN, (ii) ion-exchange resin (H+ form), H2O, (iii) aq. HClO4; Multistep reaction;

iodacetamide (144-48-9) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-carbamoylmethyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

10-(2-bromo-propyl)-10H-phenothiazine (40256-10-8) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-((Ξ)-1-methyl-2-phenothiazin-10-yl-ethyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester (26352-26-1)

Conditions	Yield
at 125℃; for 22h;

2-phenethyl iodide (17376-04-4) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-phenethyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

oxiranyl-methanol (556-52-5) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-((Ξ)-2,3-dihydroxy-propyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

cyclohexane-1,2-epoxide (286-20-4) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-((1Ξ)-ξ-2-hydroxy-cyclohexyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In methanol at 100℃; for 16h;

ammonium thiocyanate (1147550-11-5) + benzoyl chloride (98-88-4) + Norscopolamine (4684-28-0) → (S)-3-hydroxy-2-phenyl-propionic acid 9-(benzoyl-thiocarbamoyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester (26352-42-1)

Conditions	Yield
(i) acetone, (ii) /BRN= 4920597/; Multistep reaction;

Norscopolamine (4684-28-0) → (R)-3-chloro-2-phenyl-propionic acid (1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
With thionyl chloride

Norscopolamine (4684-28-0) + ethyl iodide (75-03-6) → (-)-N-Ethylnorscopolamin (67009-40-9)

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

Norscopolamine (4684-28-0) + 1-iodo-propane (107-08-4) → (S)-3-hydroxy-2-phenyl-propionic acid 9-propyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester (88644-35-3)

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

Norscopolamine (4684-28-0) + 1-Iodohexane (638-45-9) → (S)-3-hydroxy-2-phenyl-propionic acid 9-hexyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In ethyl acetate at 100℃; for 15h;

Norscopolamine (4684-28-0) + ethyl bromoacetate (105-36-2) → (S)-3-hydroxy-2-phenyl-propionic acid 9-ethoxycarbonylmethyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl ester

Conditions	Yield
In ethyl acetate at 80℃; for 4h;

Norscopolamine (4684-28-0) + ethylene dibromide (106-93-4) → (S)-3-hydroxy-2-phenyl-propionic acid 9,9'-ethane-1,2-diyl-bis-((1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7t-yl) ester

Conditions	Yield
In ethyl acetate at 100℃; for 100h;

Upstream product

• 5027-68-9 (S)-3-acetoxy-2-phenyl-propionic acid (1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 25645-57-2 (-)-N-Chlorformyl-O-acetylnorscopolamin 
• 25650-60-6 (S)-3-hydroxy-2-phenyl-propionic acid 9-formyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester; hydrochloride 
• 51-34-3 scopolamine 
• 6820-79-7 9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]non-7-yl-3'-(acetyloxy)-2'-phenyl propanoate 
• 25650-58-2 (-)-Formylnorscopollamin 
• 114-49-8 hyoscine hydrobromide 

Downstream Products

• 26352-43-2 (S)-3-hydroxy-2-phenyl-propionic acid 9-(acetyl-thiocarbamoyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 26352-41-0 (S)-3-hydroxy-2-phenyl-propionic acid 9-butylcarbamoyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 124065-21-0 (-)-N-(iminomethyl)norscopolamine hydrochloride 
• 26352-39-6 (S)-3-hydroxy-2-phenyl-propionic acid 9-ethylcarbamoyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 26516-79-0 (S)-3-hydroxy-2-phenyl-propionic acid 9-methylcarbamoyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 88644-35-3 (S)-3-hydroxy-2-phenyl-propionic acid 9-propyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 67009-40-9 (-)-N-Ethylnorscopolamin 
• 26352-42-1 (S)-3-hydroxy-2-phenyl-propionic acid 9-(benzoyl-thiocarbamoyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 26352-26-1 (S)-3-hydroxy-2-phenyl-propionic acid 9-((Ξ)-1-methyl-2-phenothiazin-10-yl-ethyl)-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]non-7t-yl ester 
• 14861-14-4 N-butylscopolamine 

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