114-49-8

Basic information

• Product Name: Scopolamine hydrobromide
• Synonyms: Benzeneacetic acid, a-(hydroxyMethyl)-, (1a,2b,4b,5a,7b)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-ylester, hydrobroMide (1:1), (aS)-;ScopolaMine-d3 HBr 3H2O;Hyosol;Tranaxine;ScopolaMine HBr Trihydrate;Scopolaminehydrobromidetrihydra;(αS)-α-(hydroxymethyl)-benzeneacetic acid-(1α,2β,4β,5α,7β)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl ester;(?)-Scopolamine hydrobromide hydrate
• CAS NO: 114-49-8
• Molecular Formula: BrH*C₁₇H₂₁NO₄
• Molecular Weight: 384.26
• EINECS: 204-050-6
• Product Categories: API;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors;Alkaloids;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Isotope Labeled Compounds;Acetylcholine receptor
• Mol File: 114-49-8.mol

Chemical Properties

• Melting Point: 195-199 °C (dry matter)(lit.)
• Boiling Point: 460.3 °C at 760 mmHg
• Flash Point: 232.2 °C
• Appearance: white to off-white/powder
• Vapor Pressure: 2.51E-10mmHg at 25°C
• Storage Temp.: Store at RT
• Solubility: H2O: 50 mg/mL
• CAS DataBase Reference: Scopolamine hydrobromide(CAS DataBase Reference)
• NIST Chemistry Reference: Scopolamine hydrobromide(114-49-8)
• EPA Substance Registry System: Scopolamine hydrobromide(114-49-8)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• RIDADR: UN 1544 6.1/PG 1
• WGK Germany: 3
• RTECS: YM4550000
• F: 3-8
• Hazardous Substances Data: 114-49-8(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

An acetylcholine antagonist. Used in treatment of motion sickness; antiemetic; antispasmodic; mydriatic; preanesthetic medicant

Definition

ChEBI: A hydrobromide that is obtained by reaction of scopolamine with hydrogen bromide.

Brand name

Isopto Hyoscine (Alcon); Transderm-Scop (Ciba-Geigy).

General Description

Different sources of media describe the General Description of 114-49-8 differently. You can refer to the following data:
1. Scopolamine hydrobromide(hyoscine hydrobromide) occurs as white orcolorless crystals or as a white, granular powder. It is odorlessand tends to effloresce in dry air. It is freely soluble inwater (1:1.5), soluble in alcohol (1:20), only slightly solublein chloroform, and insoluble in ether.Scopolamine is a competitive blocking agent of theparasympathetic nervous system as is atropine, but it differsmarkedly from atropine in its action on the higher nervecenters. Both drugs readily cross the blood-brain barrierand, even at therapeutic doses, cause confusion, particularlyin the elderly.
2. Colorless crystals or white powder or solid. Has no odor. pH (of 5% solution): 4-5.5. Slightly efflorescent in dry air. Bitter, acrid taste.

Air & Water Reactions

Sensitive to air, light and moisture. Water soluble.

Reactivity Profile

Scopolamine hydrobromide is incompatible with acids, bases and oxidizing agents. .

Fire Hazard

Flash point data for Scopolamine hydrobromide are not available; however, Scopolamine hydrobromide is probably combustible.

Biological Activity

Non-selective muscarinic antagonist. Widely used clinically to treat motion sickness.

Clinical Use

A sufficiently large dose of scopolamine will cause an individualto sink into a restful, dreamless sleep for about8 hours, followed by a period of approximately the samelength in which the patient is in a semiconscious state.During this time, the patient does not remember events thattake place. When scopolamine is administered with morphine,this temporary amnesia is termed twilight sleep.

Drug interactions

Potentially hazardous interactions with other drugs None known

Metabolism

Hyoscine hydrobromide is almost entirely metabolised, probably in the liver; only a small proportion of an oral dose is excreted unchanged in the urine. In one study in man, 3.4% of a single dose, administered by subcutaneous injection was excreted unchanged in urine within 72 hours.

Purification Methods

The hydrobromide is recrystallised from Me2CO, H2O or EtOH/Et2O and dried. It is soluble in H2O (60%) and EtOH (5%) but insoluble in Et2O and slightly in CHCl3. The hydrochloride has m 300o (from Me2CO). The free base is a viscous liquid which forms a crystalline hydrate with m 59o and [] D 20 -28o (c 2.7, H2O). It hydrolyses in dilute acid or base. [Meinwald J Chem Soc 712 1953, Fodor Tetrahedron 1 86 1957, Beilstein 6 III 4185.]

InChI:InChI=1/C17H21NO4.BrH/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10;/h2-6,11-16,19H,7-9H2,1H3;1H/t11-,12-,13+,14?,15-,16?;/m1./s1

Synthetic route

hyoscine hydrobromide (114-49-8) + L-proline (147-85-3) → pyrrolidine-2-carboxylic acid 2-(9-methyl-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7-yloxycarbonyl)-2-phenyl-ethyl ester

Conditions	Yield
at 120℃; for 7h;	95%

acetic anhydride (108-24-7) + hyoscine hydrobromide (114-49-8) → 9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]non-7-yl-3'-(acetyloxy)-2'-phenyl propanoate (6820-79-7)

Conditions	Yield
With sodium carbonate 1.) 2 h, 110 deg C - 115 deg C; 2.) water;	89.8%

piperidine (110-89-4) + hyoscine hydrobromide (114-49-8) → 2-phenyl-3-piperidin-1-yl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7-yl ester

Conditions	Yield
at 120℃; for 7h;	88%

hyoscine hydrobromide (114-49-8) → scopine (498-45-3)

Conditions	Yield
With sodium tetrahydroborate In ethanol at 20℃; Cooling with ice;	87%

hyoscine hydrobromide (114-49-8) → (-)-Norscopolamin-hydrochlorid (24676-80-0)

Conditions	Yield
With hydrogenchloride; potassium permanganate; sulfuric acid; sodium carbonate 1.) (pH=7), 30 deg C, water, 2 h; 2.) (pH=5-6), T < 20 deg C, CH2Cl2;	77.3%

morpholine (110-91-8) + hyoscine hydrobromide (114-49-8) → 3-morpholin-4-yl-2-phenyl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7-yl ester

Conditions	Yield
at 120℃; for 7h;	70%

hyoscine hydrobromide (114-49-8) → (3S,6S,2'S)-6β-hydroxyhyoscyamine (55869-99-3) + (3R,6R,2'S)-6β-hydroxyhyoscyamine (126371-43-5) + Hyoscyamine (101-31-5)

Conditions	Yield
With hydrogen; Nickel Raney W1	A 41.7% B 33.9% C 19.7%

hyoscine hydrobromide (114-49-8) + diethylamine (109-89-7) → 3-diethylamino-2-phenyl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7-yl ester

Conditions	Yield
at 120℃; for 7h;	10%

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;

hyoscine hydrobromide (114-49-8) → (-)-Formylnorscopollamin (25650-58-2)

Conditions	Yield
With potassium permanganate; potassium carbonate
Multi-step reaction with 4 steps 1: 89.8 percent / 2.) Na2CO3 / 1.) 2 h, 110 deg C - 115 deg C; 2.) water 2: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT 3: H2O / 1 h / 93 °C 4: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C View Scheme

acetic anhydride (108-24-7) + hyoscine hydrobromide (114-49-8) → (-)-O-Acetylscopolamin-hydrobromid (5027-67-8)

Conditions	Yield
at 100 - 115℃; for 2h; Yield given;

acetic anhydride (108-24-7) + hyoscine hydrobromide (114-49-8) → acetyl-l-scopolamine

Conditions	Yield
at 95℃;

hyoscine hydrobromide (114-49-8) → (-)-N-Chlorformyl-O-acetylnorscopolamin (25645-57-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89.8 percent / 2.) Na2CO3 / 1.) 2 h, 110 deg C - 115 deg C; 2.) water 2: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT View Scheme

hyoscine hydrobromide (114-49-8) → (-)-N-Ethylnorscopolamin-hydrochlorid (22235-93-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77.3 percent / 1.) Na2CO3, 1N H2SO4, KMnO4, 2.) HCl / 1.) (pH=7), 30 deg C, water, 2 h; 2.) (pH=5-6), T < 20 deg C, CH2Cl2 2: 91.2 percent / 1.) Na2CO3; 2.) HCl / 1.) CH3CN, 8 h, reflux; 2.) ether, MeOH View Scheme

hyoscine hydrobromide (114-49-8) → (-)-Azoniaspiro-(norscopolamin-8,1'-pyrrolidin)-bromid (26352-27-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: KMnO4, Na2CO3, 1N H2SO4 / H2O / 2 h / 30 °C / (pH=7) 2: 80.1 percent / acetonitrile / 25 h / 80 °C View Scheme
Multi-step reaction with 6 steps 1: 89.8 percent / 2.) Na2CO3 / 1.) 2 h, 110 deg C - 115 deg C; 2.) water 2: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT 3: H2O / 1 h / 93 °C 4: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C 5: 20percent HCl 6: 80.1 percent / acetonitrile / 25 h / 80 °C View Scheme
Multi-step reaction with 5 steps 1: 89.8 percent / 2.) Na2CO3 / 1.) 2 h, 110 deg C - 115 deg C; 2.) water 2: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT 3: H2O / 1 h / 93 °C 4: 1.) 36percent HCl; 2.) NaOH / 1.) H2O, 2 h, RT; 2.) H2O, 10 deg C to 15 deg C 5: 80.1 percent / acetonitrile / 25 h / 80 °C View Scheme

hyoscine hydrobromide (114-49-8) → (-)-N-Ethylnorscopolamin (67009-40-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77.3 percent / 1.) Na2CO3, 1N H2SO4, KMnO4, 2.) HCl / 1.) (pH=7), 30 deg C, water, 2 h; 2.) (pH=5-6), T < 20 deg C, CH2Cl2 2: Na2CO3 / acetonitrile / 8 h / Heating View Scheme

hyoscine hydrobromide (114-49-8) → (-)-O-Acetylnorscopolamin-hydrochlorid

Conditions	Yield
Multi-step reaction with 3 steps 1: 89.8 percent / 2.) Na2CO3 / 1.) 2 h, 110 deg C - 115 deg C; 2.) water 2: 81.2 percent / toluene / 1.) 5 h, RT; 2.) 4 d, RT 3: H2O / 1 h / 93 °C View Scheme

hyoscine hydrobromide (114-49-8) → (1R,2R,4S,5S,7S)-9,9-Diethyl-7-((S)-3-hydroxy-2-phenyl-propionyloxy)-3-oxa-9-azonia-tricyclo[3.3.1.02,4]nonane; bromide (41749-07-9, 150521-04-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 77.3 percent / 1.) Na2CO3, 1N H2SO4, KMnO4, 2.) HCl / 1.) (pH=7), 30 deg C, water, 2 h; 2.) (pH=5-6), T < 20 deg C, CH2Cl2 2: Na2CO3 / acetonitrile / 8 h / Heating 3: acetonitrile / Ambient temperature View Scheme

hyoscine hydrobromide (114-49-8) → (1R,2R,4S,5S,7S)-9-Allyl-9-ethyl-7-((S)-3-hydroxy-2-phenyl-propionyloxy)-3-oxa-9-azonia-tricyclo[3.3.1.02,4]nonane; bromide (30269-62-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 77.3 percent / 1.) Na2CO3, 1N H2SO4, KMnO4, 2.) HCl / 1.) (pH=7), 30 deg C, water, 2 h; 2.) (pH=5-6), T < 20 deg C, CH2Cl2 2: Na2CO3 / acetonitrile / 8 h / Heating 3: acetonitrile / Ambient temperature View Scheme

hyoscine hydrobromide (114-49-8) → oxytropium bromide (30286-75-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 77.3 percent / 1.) Na2CO3, 1N H2SO4, KMnO4, 2.) HCl / 1.) (pH=7), 30 deg C, water, 2 h; 2.) (pH=5-6), T < 20 deg C, CH2Cl2 2: Na2CO3 / acetonitrile / 8 h / Heating 3: 84.6 percent / acetonitrile / 68 h / Ambient temperature View Scheme

hyoscine hydrobromide (114-49-8) → 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
Multi-step reaction with 2 steps 1: (i) Ac2O, (ii) aq. Na2CO3, KMnO4, (iii) aq. HCl 2: (i) Et3N, MeCN, (ii) ion-exchange resin (H+ form), H2O, (iii) aq. HClO4 View Scheme

hyoscine hydrobromide (114-49-8) → 7't-((S)-3-hydroxy-2-phenyl-propionyloxy)-(1'rN,2'tH,4'tH,5'cN)-spiro[morpholinium-4,9'-(3-oxa-9-aza-tricyclo[3.3.1.02,4]nonanium)]; perchlorate

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) Ac2O, (ii) aq. Na2CO3, KMnO4, (iii) aq. HCl 2: (i) Et3N, MeCN, (ii) ion-exchange resin (H+ form), H2O, (iii) aq. HClO4, iPrOH View Scheme

hyoscine hydrobromide (114-49-8) → 7't-((S)-3-hydroxy-2-phenyl-propionyloxy)-1,3-dihydro-(1'rN,2'tH,4'tH,5'cN)-spiro[isoindolium-2,9'-(3-oxa-9-aza-tricyclo[3.3.1.02,4]nonanium)]; perchlorate

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) Ac2O, (ii) aq. Na2CO3, KMnO4, (iii) aq. HCl 2: (i) Et3N, MeCN, (ii) ion-exchange resin (H+ form), H2O, (iii) aq. HClO4, iPrOH View Scheme

hyoscine hydrobromide (114-49-8) → (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
Multi-step reaction with 2 steps 1: aq. KMnO4, K2CO3 2: SOCl2 View Scheme

hyoscine hydrobromide (114-49-8) → scopolamine (51-34-3, 138-12-5, 64069-63-2, 124917-17-5)

Conditions	Yield
With sodium carbonate In water; ethyl acetate at 0℃; for 0.25h; Reagent/catalyst;	0.6 g
With sodium hydroxide In water pH=10; Inert atmosphere;
With sodium hydroxide In water pH=10;

hyoscine hydrobromide (114-49-8) → [2H9]-[7(S)-(1α,2β,4β,5α,7β)]-9-butyl-7-(3-hydroxy-1-oxo-2-phenyl-propoxy)-9-methyl-3-oxa-9-azatricylco[3.3.1.02,4]nonane bromide

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate / water; ethyl acetate / 0.25 h / 0 °C 2: acetonitrile / 264 h / 60 °C / Sealed tube View Scheme

hyoscine hydrobromide (114-49-8) → [14C]-[7(S)-(1α,2β,4β,5α,7β)]-9-butyl-7-(3-hydroxy-1-oxo-2-phenyl-propoxy)-9-methyl-3-oxa-9-azatricylco[3.3.1.02,4]nonane bromide

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate / water; ethyl acetate / 0.25 h / 0 °C 2: acetonitrile / 504 h / 55 °C / Sealed tube View Scheme

hyoscine hydrobromide (114-49-8) → (2S)-(1S,2S,7R)-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl 3-((tert-butyldimethylsilyl)oxy)-2-phenylpropanoate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / pH 10 / Inert atmosphere 2.1: 1H-imidazole / dichloromethane / 20 - 25 °C / Inert atmosphere 3.1: tri(4-tolyl)aminium hexafluorophosphate; 1,4-diaza-bicyclo[2.2.2]octane / acetonitrile / -5 °C / Inert atmosphere 3.2: phenylzinc halide / 0 °C / Inert atmosphere View Scheme

hyoscine hydrobromide (114-49-8) → (1R,2R,4S,5S,7r)-ethyl 7-(benzoyloxy)-3-oxa-9-azatricyclo[3.3.1.02,4]nonane-9-carboxylate

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate / ethanol / 20 °C / Cooling with ice 2: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / -35 - 20 °C 3: potassium carbonate / chloroform / Inert atmosphere; Reflux View Scheme

Downstream Products

• 4684-28-0 Norscopolamine 
• 25650-58-2 (-)-Formylnorscopollamin 
• 5027-67-8 (-)-O-Acetylscopolamin-hydrobromid 
• 6820-79-7 9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]non-7-yl-3'-(acetyloxy)-2'-phenyl propanoate 
• 24676-80-0 (-)-Norscopolamin-hydrochlorid 
• 55869-99-3 (3S,6S,2'S)-6β-hydroxyhyoscyamine 
• 126371-43-5 (3R,6R,2'S)-6β-hydroxyhyoscyamine 
• 101-31-5 Hyoscyamine 
• 51-34-3 scopolamine 
• 139404-48-1 tiotropium bromide 
• 498-45-3 scopine 

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An accurate, simple, reproducible and sensitive method for the determination of atropine sulfate and scopolamine hydrobromide has been developed and validated. Atropine sulfate and scopolamine hydrobromide were separated using a μBondapack C18 column by isocratic elution with flow rate 1.0 ml/m...detailed

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