498-45-3

Basic information

• Product Name: Scopine
• Synonyms: SCOPINE;(1alpha,2beta,4beta,5alpha,7beta)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02.4]nonan-7-ol;SCOPINE, 97+%;(1α,2β,4β,5α)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7β-ol;(1β,2α,4α,5β,7α)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-ol;(1R,2R,4S,5S,7s)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-ol;3-Oxa-9-azatricyclo[3.3.1.02,4]nonan-7-ol,9-Methyl-, (1a,2b,4b,5a,7b)-
• CAS NO: 498-45-3
• Molecular Formula: C₈H₁₃NO₂
• Molecular Weight: 155.19
• EINECS: 102-503-4
• Product Categories: API intermediates;Tiotropium Bromide Intermediates;Inhibitors
• Mol File: 498-45-3.mol
• Article Data: 7

Chemical Properties

• Melting Point: 73.0 to 77.0 °C
• Boiling Point: 281.3oC at 760 mmHg
• Flash Point: 123.9oC
• Appearance: /
• Density: 1.284 g/cm3
• Vapor Pressure: 0.000427mmHg at 25°C
• Refractive Index: 1.573
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: Dichloromethane; Methanol
• PKA: 14?+-.0.20(Predicted)
• CAS DataBase Reference: Scopine(CAS DataBase Reference)
• NIST Chemistry Reference: Scopine(498-45-3)
• EPA Substance Registry System: Scopine(498-45-3)

Safety Data

• Hazardous Substances Data: 498-45-3(Hazardous Substances Data)

Usage

Uses

Scopin is an Intermediate in the synthesis of Scopine Methobromide (Tiotropium EP Impurity G) (S199985), an impurity of Tiotropium (T444850), an muscarinic receptor antagonist and bronchodilator.

Biological Activity

scopine is the metabolite of anisodine, which is a α1-adrenergic receptor agonist and used in the treatment of acute circulatory shock.

InChI:InChI=1/C8H13NO2/c1-9-5-2-4(10)3-6(9)8-7(5)11-8/h4-8,10H,2-3H2,1H3/t4?,5-,6+,7-,8+

Synthetic route

scopolamine (51-34-3, 138-12-5, 64069-63-2, 124917-17-5) → scopine (498-45-3)

Conditions	Yield
With 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In toluene at 25℃; for 48h;	99.3%
Stage #1: scopolamine With sodium tetrahydroborate In ethanol at 0 - 20℃; for 24h; Stage #2: With hydrogenchloride In diethyl ether; ethanol at 20℃; for 24h;	50%
With ammonium chloride; ammonia at 30℃;

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

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

scopine t-butyldimethylsilyl ether (182054-94-0) → scopine (498-45-3)

Conditions	Yield
With tert-butyl-ammonium fluoride	82%
With tetrabutyl ammonium fluoride In tetrahydrofuran for 18h;	81%

scopine benzyl ether (132622-34-5, 132697-33-7) → scopine (498-45-3)

Conditions	Yield
With hydrogenchloride; hydrogen; potassium carbonate; palladium on activated charcoal 1) EtOH, 5 atm, r.t, 12h; Yield given. Multistep reaction;

(-)-scopolamine → scopine (498-45-3)

Conditions	Yield
With NH3-NH4Cl-buffer solution
With bis-1-chloroethyl ether anschliessende Hydrolyse mit wss. Ba(OH)2 und dann mit wss. HCl;

O-acetyl-scopine → scopine (498-45-3)

Conditions	Yield
With sodium hydroxide; acetone

Tropilidenoxid (33250-14-5) → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 8 steps 1: LiAlH4 / diethyl ether / 1 h 2: Me4N(1+)IO4(1-) / CH2Cl2 3: 1.) Me4N(1+)*IO4(1-), 2.) Imidazole, 3.) Na(Hg), Na3PO4, 4.) MCPBA 4: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 5: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 6: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 7: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 8: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

cyclohepta-3,5-dien-1-ol (1121-63-7) → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: Me4N(1+)IO4(1-) / CH2Cl2 2: 1.) Me4N(1+)*IO4(1-), 2.) Imidazole, 3.) Na(Hg), Na3PO4, 4.) MCPBA 3: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 4: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 5: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 6: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 7: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme
Multi-step reaction with 9 steps 1: NaH / tetrahydrofuran / 15 h / 50 °C 2: 63 percent / LiCl, p-benzoquinone, glacial acetic acid / Pd(OAc)2 / acetic acid / 36 h 3: 96 percent / DIBAL / tetrahydrofuran; hexane / 0.75 h / 2 °C 4: 66 percent / Pd(PPh3)4 / acetonitrile / 4 h 5: 76 percent / LiCl, MsCl, 2,4,6-trimethylpyridine / dimethylformamide / 0 deg C to r.t., overnight 6: 86 percent / m-CPBA / CH2Cl2 / 48 h / Ambient temperature 7: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 8: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 9: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

Cyclohepta-1,3,5-triene (544-25-2) + norcaradiene-(2.4) → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 9 steps 1: aq. CH3COOOH, Na2CO3 / CH2Cl2 / 3 h / 0 °C 2: LiAlH4 / diethyl ether / 1 h 3: Me4N(1+)IO4(1-) / CH2Cl2 4: 1.) Me4N(1+)*IO4(1-), 2.) Imidazole, 3.) Na(Hg), Na3PO4, 4.) MCPBA 5: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 6: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 7: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 8: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 9: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

1β-hydroxy-4β-<(benzyloxycarbonyl)amino>-6-<(t-butyldimethylsilyl)oxy>cyclohept-2-ene → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 68 percent / MCPBA / CH2Cl2 / 3 h / Ambient temperature 2: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 3: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 4: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 5: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 6: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme
Multi-step reaction with 6 steps 1: MCPBA / CH2Cl2 / 3 h / Ambient temperature 2: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 3: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 4: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 5: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 6: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

N-benzyloxycarbonyl-3α-<(t-butyldimethylsilyl)oxy>-6β,7β-epoxy-8-azabicyclo<3.2.1>octane (182054-91-7) → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 2: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

1β-hydroxy-2β,3β-epoxy-4β-<(benzyloxycarbonyl)amino>-6α-<(t-butyldimethylsilyl)oxy>cycloheptane → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 2: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 3: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 4: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 5: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

1α-chloro-2β,3β-epoxy-4β-<(benzyloxycarbonyl)amino>-6α-<(t-butyldimethylsilyl)oxy>cycloheptane → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 2: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 3: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

1β-<(p-toluenesulphonyl)oxy>-2β,3β-epoxy-4β-<(benzyloxycarbonyl)amino>-6α-<(t-butyldimethylsilyl)oxy>cycloheptane → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 2: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 3: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 4: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

N-benzyloxycarbonyl-3α-hydroxy-6-aza-7-oxabicyclo[3.2.2]non-8-ene → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 6 steps 1: 1.) Me4N(1+)*IO4(1-), 2.) Imidazole, 3.) Na(Hg), Na3PO4, 4.) MCPBA 2: 1.) n-BuLi / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, RT, 1.5 h 3: 64 percent / LiCl / dimethylsulfoxide / 1.5 h / 55 °C 4: 82 percent / NaH / tetrahydrofuran; 1,2-dimethoxy-ethane / 3 h / 20 - 50 °C 5: 95 percent / LiAlH4 / diethyl ether / 2 h / Heating 6: 81 percent / TBAF / tetrahydrofuran / 18 h View Scheme

6-(benzyloxy)-1,3-cycloheptadiene (115522-58-2) → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 8 steps 1: 63 percent / LiCl, p-benzoquinone, glacial acetic acid / Pd(OAc)2 / acetic acid / 36 h 2: 96 percent / DIBAL / tetrahydrofuran; hexane / 0.75 h / 2 °C 3: 66 percent / Pd(PPh3)4 / acetonitrile / 4 h 4: 76 percent / LiCl, MsCl, 2,4,6-trimethylpyridine / dimethylformamide / 0 deg C to r.t., overnight 5: 86 percent / m-CPBA / CH2Cl2 / 48 h / Ambient temperature 6: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 7: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 8: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

1β-hydroxy-4β-chloro-6α-(benzyloxy)-2-cycloheptene (132622-29-8) → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 6 steps 1: 66 percent / Pd(PPh3)4 / acetonitrile / 4 h 2: 76 percent / LiCl, MsCl, 2,4,6-trimethylpyridine / dimethylformamide / 0 deg C to r.t., overnight 3: 86 percent / m-CPBA / CH2Cl2 / 48 h / Ambient temperature 4: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 5: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 6: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

1β-acetoxy-4β-chloro-6α-(benzyloxy)-2-cycloheptene (115522-57-1, 150338-86-6) → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 7 steps 1: 96 percent / DIBAL / tetrahydrofuran; hexane / 0.75 h / 2 °C 2: 66 percent / Pd(PPh3)4 / acetonitrile / 4 h 3: 76 percent / LiCl, MsCl, 2,4,6-trimethylpyridine / dimethylformamide / 0 deg C to r.t., overnight 4: 86 percent / m-CPBA / CH2Cl2 / 48 h / Ambient temperature 5: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 6: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 7: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

1β-(p-toluenesulfonamido)-4-chloro-6α-(benzyloxy)-2-cycloheptene (132622-31-2, 132697-30-4) → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 86 percent / m-CPBA / CH2Cl2 / 48 h / Ambient temperature 2: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 3: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 4: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

1β-(p-toluenesulfonamido)-2β,3β-epoxy-4α-chloro-6α-(benzyloxy)-2-cycloheptene (132622-32-3) → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 2: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 3: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

1β-(p-toluenesulfonamido)-4β-hydroxy-6α-(benzyloxy)-2-cycloheptene (132622-30-1, 132697-31-5) → scopine (498-45-3)

Conditions

Yield

Multi-step reaction with 5 steps 1: 76 percent / LiCl, MsCl, 2,4,6-trimethylpyridine / dimethylformamide / 0 deg C to r.t., overnight 2: 86 percent / m-CPBA / CH2Cl2 / 48 h / Ambient temperature 3: 95 percent / K2CO3 / methanol / 56 h / Ambient temperature 4: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 5: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

3α-(benzyloxy)-6β,7β-epoxy-8-(p-toluenesulfonyl)-1β-azabicyclo<3.2.1>octane (132622-33-4, 132697-32-6) → scopine (498-45-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) naphthalene, Na / 1) THF, -78 deg C, 30 min 2: 1) aq.2M HCl, H2, 2) 10percent aq. K2CO3 / 1) 10percent Pd/C / 1) EtOH, 5 atm, r.t, 12h View Scheme

hyoscine-N-butyl bromide (149-64-4) → scopine (498-45-3)

Conditions	Yield
With ruthenium trichloride; potassium metaperiodate; diperiodatocuprate(III) dihydrate; water; potassium nitrate; potassium hydroxide at 28℃; for 6h; Kinetics; Catalytic behavior; Concentration; Temperature; Inert atmosphere;

scopine (498-45-3) + methyl iodide (74-88-4) → (1R,2R,4S,5S,7S)-7-hydroxy-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-9-iumiodide (N-methylscopinium) (21662-36-2)

Conditions	Yield
In dichloromethane at 20℃; for 48h; Inert atmosphere;	85%

2,2-di(thiophen-2-yl)acetic acid (4408-82-6) + scopine (498-45-3) → C18H19NO3S2 (1336913-21-3)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; Product distribution / selectivity;	83%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; Reagent/catalyst; Solvent; Concentration;	83%
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; Product distribution / selectivity;

scopine (498-45-3) + chlorambucil (305-03-3) → C22H30Cl2N2O3

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h;	82.3%

hydroxy-di-thiophen-2-yl-acetic acid methyl ester (26447-85-8) + scopine (498-45-3) → N-demethyltiotropium (136310-64-0)

Conditions	Yield
With potassium tert-butylate; 1-butyl-3-methylimidazolium Tetrafluoroborate In tetrahydrofuran at 20℃; for 18h; Solvent; Concentration; Reagent/catalyst; Temperature; Time; Molecular sieve;	73%
Stage #1: hydroxy-di-thiophen-2-yl-acetic acid methyl ester; scopine at 70℃; under 210 Torr; for 1h; Stage #2: With sodium hydride at 70℃; under 210 Torr; for 3h;	42%
With sodium hydride In toluene; mineral oil at 90℃; for 2h;	33%
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 70℃; under 15.0015 Torr; for 19h;

benzoic acid (65-85-0) + scopine (498-45-3) → (1R,2R,4S,5S,7r)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl benzoate

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -35 - 20℃;	67.9%

hydroxy-di-thiophen-2-yl-acetic acid methyl ester (26447-85-8) + scopine (498-45-3) → N-demethyltiotropium (136310-64-0) + scopoline + di-(2-thienyl)glycolic acid scopoline ester

Conditions	Yield
Stage #1: hydroxy-di-thiophen-2-yl-acetic acid methyl ester; scopine With sodium t-butanolate In tetrahydrofuran; toluene at 70 - 90℃; under 375.038 Torr; for 4.41667h; Inert atmosphere; Stage #2: With hydrogenchloride In dichloromethane; water Cooling with ice; Stage #3: With sodium carbonate In water Reagent/catalyst; Solvent; Time; Temperature; Pressure; Concentration; Overall yield = 37.2 g;	A 58% B 5.3 %Chromat. C 6.1 %Chromat.
Stage #1: hydroxy-di-thiophen-2-yl-acetic acid methyl ester; scopine With potassium tert-butylate In toluene at 70 - 90℃; under 225.023 - 300.03 Torr; for 4.25h; Inert atmosphere; Stage #2: With hydrogenchloride In dichloromethane; water Cooling with ice; Stage #3: With sodium carbonate In water Reagent/catalyst; Temperature; Time; Overall yield = 0.82 g;	A 41% B 18.4 %Chromat. C 5.6 %Chromat.
Stage #1: hydroxy-di-thiophen-2-yl-acetic acid methyl ester; scopine With sodium hydride In toluene; mineral oil at 70 - 90℃; under 225.023 - 300.03 Torr; for 4.25h; Inert atmosphere; Stage #2: With hydrogenchloride In water; toluene; mineral oil Cooling with ice; Stage #3: With sodium carbonate In water Overall yield = 1.01 g;	A 21% B 35.7 %Chromat. C 30.4 %Chromat.

2,2-diphenylpropionyl chloride (40997-78-2) + scopine (498-45-3) → scopine 2,2-diphenylpropionate

Conditions	Yield
In dichloromethane at 40℃; for 24h;	47%

hydroxy-di-thiophen-2-yl-acetic acid methyl ester (26447-85-8) + scopine (498-45-3) → N-demethyltiotropium (136310-64-0) + scopoline

Conditions	Yield
Stage #1: hydroxy-di-thiophen-2-yl-acetic acid methyl ester; scopine With sodium t-butanolate In toluene at 70 - 90℃; under 225.023 - 300.03 Torr; for 4.25h; Inert atmosphere; Stage #2: With hydrogenchloride In dichloromethane; water Cooling with ice; Stage #3: With sodium carbonate In water Time; Concentration;	A 33% B 26.3 %Chromat.
Stage #1: hydroxy-di-thiophen-2-yl-acetic acid methyl ester; scopine With sodium methylate In toluene at 70 - 90℃; under 75.0075 - 225.023 Torr; for 5.25h; Inert atmosphere; Stage #2: With hydrogenchloride In water; toluene Cooling with ice; Stage #3: With sodium carbonate In water	A 11.6 %Chromat. B 57.3 %Chromat.

bis(trichloromethyl) carbonate (32315-10-9) + 2-amino-5-fluorobiphenyl (1717-22-2) + scopine (498-45-3) → (1R,2R,4S,5S,7s,9r)-7-(((5-fluorobiphenyl-2-yl)carbamoyl)oxy)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-9-ium chloride

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; scopine In acetonitrile at 0 - 20℃; for 36h; Stage #2: 2-amino-5-fluorobiphenyl With pyridine at 60℃; for 24h;	8%

1-chloro-4-(diazo(phenyl)methyl)benzene (1140-33-6) + scopine (498-45-3) → 7t-(4-chloro-benzhydryloxy)-9-methyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]nonane (116603-25-9)

Conditions	Yield
In benzene at 95 - 100℃; for 5.5h;

diazodiphenylmethane (908093-98-1) + scopine (498-45-3) → 7t-benzhydryloxy-9-methyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.02,4]nonane (112018-04-9)

Conditions	Yield
In benzene at 80 - 85℃; for 3h;

3-acetoxy-2-phenyl-propionyl chloride (14510-37-3) + nitrobenzene (98-95-3) + scopine (498-45-3) → (+-)-O-acetyl-scopolamine hydrochloride

pyridine (110-86-1) + scopine (498-45-3) + CrO3 → 6exo,7exo-epoxy-tropan-3-one (498-47-5) + (+-)-N-formyl-norscopolin

scopine (498-45-3) → dl-scopolin

Conditions	Yield
bei der Destillation;

scopine (498-45-3) + Cr2O3-H2SO4 → dl-scopolin

Conditions	Yield
at 50 - 60℃;

scopine (498-45-3) + n KOH-solution → dl-scopolin

Conditions	Yield
at 20℃;

3-acetoxy-2-phenyl-propionyl chloride (14510-37-3) + nitrobenzene (98-95-3) + scopine (498-45-3) → O-<3-acetoxy-2-phenyl-propionyl>-scopolamine hydrochloride

3-acetoxy-2-phenyl-propionyl chloride (14510-37-3) + scopine (498-45-3) → O-acetyl-scopine hydrochloride + O-<3-acetoxy-2-phenyl>-propionyl>-scopolamine hydrochloride

scopine (498-45-3) → salts of scopolin

chlorosulfonic acid (7790-94-5) + scopine (498-45-3) → scopinesulfuric acid + dl-scopolinsulfuric acid

Upstream product

• 33250-14-5 Tropilidenoxid 
• 115522-57-1 1β-acetoxy-4β-chloro-6α-(benzyloxy)-2-cycloheptene 
• 149-64-4 hyoscine-N-butyl bromide 
• 114-49-8 hyoscine hydrobromide 
• 132622-33-4 3α-(benzyloxy)-6β,7β-epoxy-8-(p-toluenesulfonyl)-1β-azabicyclo<3.2.1>octane 
• 132622-30-1 1β-(p-toluenesulfonamido)-4β-hydroxy-6α-(benzyloxy)-2-cycloheptene 
• 132622-32-3 1β-(p-toluenesulfonamido)-2β,3β-epoxy-4α-chloro-6α-(benzyloxy)-2-cycloheptene 
• 132622-31-2 1β-(p-toluenesulfonamido)-4-chloro-6α-(benzyloxy)-2-cycloheptene 
• 132622-29-8 1β-hydroxy-4β-chloro-6α-(benzyloxy)-2-cycloheptene 
• 115522-58-2 6-(benzyloxy)-1,3-cycloheptadiene 
• 182054-91-7 N-benzyloxycarbonyl-3α-<(t-butyldimethylsilyl)oxy>-6β,7β-epoxy-8-azabicyclo<3.2.1>octane 
• 544-25-2 Cyclohepta-1,3,5-triene 
• 1121-63-7 cyclohepta-3,5-dien-1-ol 
• 182054-94-0 scopine t-butyldimethylsilyl ether 

Downstream Products

• 116603-25-9 7t-(4-chloro-benzhydryloxy)-9-methyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]nonane 
• 112018-04-9 7t-benzhydryloxy-9-methyl-(1rN,2tH,4tH,5cN)-3-oxa-9-aza-tricyclo[3.3.1.0^2,4]nonane 
• 139404-48-1 tiotropium bromide 
• 136310-64-0 N-demethyltiotropium 
• 646530-82-7 scopoline 

Relevant articles and documents

Kinetic and mechanistic study of Ru(III) catalysed oxidation of anti-cholinergic drug hyoscinebutylbromide by diperiodatocuprate(III) in aqueous alkaline medium

Hyoscine butyl bromide (HBB) is an anti-cholinergic and anti-muscarinic drug used to treat pain and discomfort caused by abdominal cramps etc. It is semi-synthetic derivative alkaloid hyoscyamine having a broad spectrum of activity. Hence the Ru(III) catalyzed the oxidation of hyoscine butyl bromide drug by diperiodatocuprate(III) (DPC) in aqueous alkaline medium was investigated and monitored spectrophotometrically (λmax = 415 nm) at a constant ionic strength of 0.1 mol dm-3 and 301 K. The reaction shows 1:2 stoichiometry between HBB and DPC. The reaction is of the first order in [DPC] and [Ru(III)] and less than unit order in [HBB] and [alkali], periodate has a retarding effect on the reaction rate. The ionic strength, dielectric constant of the medium and added products has no significant effect on the rate of the reaction but Ru(III) increases the reaction rate. The main oxidation products of HBB were identified by spectral studies. The active forms of catalyst and oxidant were detected as Ru(III), [Cu(H2IO6)(H2O)2] respectively. The rate law and reaction mechanism was proposed. The equilibrium constants and rate constants were calculated. The activation parameters were deliberated for catalyzed and uncatalyzed reactions.

IMPROVED PROCESS FOR ACYL TRANSFER REACTIONS

The present invention relates to a novel process for the preparation of esters like Aclidinium, Atropin, Glycopyrroniunn, Tiotropium, Trospium and their respective precursors and derivatives, based on direct acyl transfer reactions.

Total synthesis of scopine, pseudoscopine, and nor-derivatives

Scopine and pseudoscopine have been synthesised from cyclohepta-3,5-dienol; the initial 1,4-functionalisation of the diene is based on a nitroso- cycloaddition. The use of the N-benzyloxycarbonyl group throughout the scheme allows ultimate reductive deprotection to yield N-methyl or novel NH (nor-) derivatives without damage to the exo-epoxide of the title compounds. Preliminary investigation of nitroso- cycloaddition to 5,6-epoxycyclohepta-1,3-diene is described.