509-66-0

Synthetic route

(+)-14β-bromocodeinone (5140-31-8) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol; chloroform under 760 Torr; for 5h; Ambient temperature;

neopinone dimethyl acetal (32398-20-2) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
With hydrogenchloride

thebaine (115-37-7) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-bromo-acetamide 2: H2, aq. NaOH / Pd-C / methanol 3: aq. HCl View Scheme
Multi-step reaction with 2 steps 1: NBS / acetone; H2O 2: H2 / Pd-C / CHCl3; methanol / 5 h / 760 Torr / Ambient temperature View Scheme

14-bromo-4,5α-epoxy-3-methoxy-17-methyl-(14ξ)-morphin-7-en-6-one; hydrochloride (28406-17-9) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
With sodium sulfite

3a(R),9b(S)-dihydro-5-methoxy-9b-<2-(N-methylammonio)ethyl>phenanthro<4,4a,4b,5-bcd>furan-3(8H)-one trifluoroacetate (102422-72-0) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + C18H19NO3 + codeinone (467-13-0)

Conditions	Yield
With sodium hydrogencarbonate In chloroform; water for 0.333333h; Yield given. Yields of byproduct given;

14-bromo-codeinone → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
With methanol; palladium on activated charcoal; chloroform

codeine hydrochloride (1422-07-7) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0)

Conditions	Yield
With alcohol dehydrogenase from Thermoanaerobium brockii; β-nicotinamide dinucleotide phosphate sodium salt; morphine dehydrogenase from Pseudomonas putida M10 In phosphate buffer at 30℃; for 24h; Title compound not separated from byproducts.;

codeine (76-57-3) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0)

Conditions	Yield
With β-nicotinamide dinucleotide phosphate sodium salt; NADP+-dependent morphine dehydrogenase; 1-(3-hydroxypropyl)-3-methylimidazolium glycolate; water In phosphate buffer at 30℃; for 24h; Title compound not separated from byproducts.;

14-bromo-4,5α-epoxy-3,6,6-trimethoxy-17-methyl-(14ξ)-morphin-7-ene (4599-09-1) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, aq. NaOH / Pd-C / methanol 2: aq. HCl View Scheme

2-iodo-6-methoxy-3-(2,2-dimethoxyethyl)phenol (916225-97-3) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: tributylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 0.5 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); triethylamine; tris-(o-tolyl)phosphine / acetonitrile / 1 h / 85 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 70 °C 3.2: 0.17 h / 20 °C 4.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 5.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 6.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 7.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 8.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 8.2: 0.5 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: tributylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 1 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine / acetonitrile / 2 h / 85 °C 3.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 4.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 5.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 6.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 7.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 7.2: 0.5 h / 20 °C View Scheme

2-iodo-4-methoxy-3-(methoxymethoxy)-1-(2-methoxyvinyl)benzene → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: acetyl chloride / methanol / 1 h / 40 °C 2.1: tributylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 0.5 h / 20 °C 3.1: tris-(dibenzylideneacetone)dipalladium(0); triethylamine; tris-(o-tolyl)phosphine / acetonitrile / 1 h / 85 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 70 °C 4.2: 0.17 h / 20 °C 5.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 6.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 7.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 8.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 9.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 9.2: 0.5 h / 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: acetyl chloride / methanol / 1 h / 40 °C 2.1: tributylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 1 h / 20 °C 3.1: tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine / acetonitrile / 2 h / 85 °C 4.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 5.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 6.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 7.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 8.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 8.2: 0.5 h / 20 °C View Scheme

benzyl 2-((5R,6R)-5-(tert-butyldimethylsilyloxy)-6-(3-(2,2-dimethoxyethyl)-2-iodo-6-methoxyphenoxy)cyclohex-1-enyl)ethylcarbamate (1257051-27-6) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); triethylamine; tris-(o-tolyl)phosphine / acetonitrile / 1 h / 85 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 70 °C 2.2: 0.17 h / 20 °C 3.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 4.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 5.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 6.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 7.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 7.2: 0.5 h / 20 °C View Scheme

benzyl N-[2-[(5aR,6R,9aS)-6-(tert-butyldimethylsilyloxy)-6,7-dihydro-1-(2,2-dimethoxyethyl)-4-methoxy-9a(5aH)-dibenzofuranyl]ethyl]carbamate (1201905-44-3) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 70 °C 1.2: 0.17 h / 20 °C 2.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 3.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 4.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 6.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 6.2: 0.5 h / 20 °C View Scheme

C32H45N3O11SSi (1201905-45-4) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 2.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 3.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 5.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 5.2: 0.5 h / 20 °C View Scheme

N-[2-[(5aR,6R,9aS)-6,7-dihydro-6-hydroxy-1-(2,2-dimethoxyethyl)-4-methoxy-9a(5aH)-dibenzofuranyl]ethyl]-N-methyl-2,4-dinitrobenzenesulfonamide (1201905-46-5) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 2.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 4.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 4.2: 0.5 h / 20 °C View Scheme

N-[2-[(5aR,9aS)-6,7-dihydro-1-(2,2-dimethoxyethyl)-4-methoxy-6-oxo-9a(5aH)-dibenzofuranyl]ethyl]-N-methyl-2,4-dinitrobenzenesulfonamide (1201905-48-7) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 3.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 3.2: 0.5 h / 20 °C View Scheme

C24H23N3O10S (1201905-49-8) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 2.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 2.2: 0.5 h / 20 °C View Scheme

N-[2-[(3aR,9RS,9bS)-3a,8,9,9a-tetrahydro-9-(methanesulfonyloxy)-5-methoxy-3-oxo-9b-phenanthro[4,5-bcd]furanyl]ethyl]-N-methyl-2,4-dinitrobenzenesulfonamide (1257051-30-1) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0)

Conditions	Yield
Stage #1: N-[2-[(3aR,9RS,9bS)-3a,8,9,9a-tetrahydro-9-(methanesulfonyloxy)-5-methoxy-3-oxo-9b-phenanthro[4,5-bcd]furanyl]ethyl]-N-methyl-2,4-dinitrobenzenesulfonamide With mercaptoacetic acid; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Stage #2: With sodium carbonate In dichloromethane; water at 20℃; for 0.5h;

C24H21N3O9S (1201905-50-1) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0)

Conditions	Yield
Stage #1: C24H21N3O9S With mercaptoacetic acid; triethylamine In dichloromethane at 0℃; for 0.5h; Stage #2: With sodium carbonate In dichloromethane; water at 20℃; for 0.5h;

N-[2-((5R,6R)-5-(tert-butyldimethylsilyloxy)-6-(3-(2,2-dimethoxyethyl)-2-iodo-6-methoxyphenoxy)cyclohex-1-enyl)]-N-methyl-2,4-dinitrobenzenesulfonamide (1257051-37-8) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine / acetonitrile / 2 h / 85 °C 2.1: camphor-10-sulfonic acid / methanol / 6 h / 20 °C 3.1: Dess-Martin periodane / dichloromethane / 0.5 h / 40 °C 4.1: trifluoroacetic acid / water; toluene / 2 h / 50 °C 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C 6.1: mercaptoacetic acid; triethylamine / dichloromethane / 0.5 h / 0 °C 6.2: 0.5 h / 20 °C View Scheme

2-((3aS,3a1S)-5-methoxy-8,9-dihydrophenanthro[4,5-bcd]furan-3a1(3aH)-yl)ethan-1-ol → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: oxygen; 5,15,10,20-tetraphenylporphyrin / dichloromethane / 4 h / 20 °C / Irradiation 2: triethylamine / dichloromethane / 0.17 h / 20 °C 3: Martins sulfurane / dichloromethane / 0.17 h / 0 °C 4: N-ethyl-N,N-diisopropylamine; thiophenol / dichloromethane / 0.67 h / 0 °C View Scheme

N-(2-((3aR,3a1S,9aS)-9a-hydroxy-5-methoxy-3-oxo-3,8,9,9a-tetrahydrophenanthro[4,5-bcd]furan-3a1(3aH)-yl)ethyl)-N-methyl-2,4-dinitrobenzenesulfonamide → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Martins sulfurane / dichloromethane / 0.17 h / 0 °C 2: N-ethyl-N,N-diisopropylamine; thiophenol / dichloromethane / 0.67 h / 0 °C View Scheme

N-(2-((3aR,3a1S)-5-methoxy-3-oxo-3,8-dihydrophenanthro[4,5-bcd]furan-3a1(3aH)-yl)ethyl)-N-methyl-2,4-dinitrobenzenesulfonamide → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0)

Conditions	Yield
With thiophenol; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.666667h; Overall yield = 50.5 %; Overall yield = 53.5 mg;

C31H34N2O6S → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0.17 h / 20 °C 2: Martins sulfurane / dichloromethane / 0.17 h / 0 °C 3: N-ethyl-N,N-diisopropylamine; thiophenol / dichloromethane / 0.67 h / 0 °C View Scheme

codeine (76-57-3) → (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0) + Neopin (467-14-1)

Conditions	Yield
With NADP In aq. buffer at 30℃; for 10.6667h; pH=9; Reagent/catalyst; Enzymatic reaction;

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) → Oxycodone (76-42-6)

Conditions	Yield
With phenylsilane; oxygen; cobalt acetylacetonate In tetrahydrofuran for 12h;	97%

methyllithium (917-54-4) + (4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) → 4,5α-epoxy-3-methoxy-6,17-dimethyl-morphin-8(14)-en-6α-ol

Conditions	Yield
In toluene

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) → isoneopine (16008-33-6)

Conditions	Yield
With sodium tetrahydroborate In methanol
With potassium hydroxide; sodium tetrahydroborate In water

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) → Neopin (467-14-1)

Conditions	Yield
With sodium tetrahydroborate In methanol
With lithium triethylborohydride In tetrahydrofuran

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + codeinone (467-13-0) → 7,8-didehydro-4-hydroxy-3-methoxy-17-methyl-morphinan-6-one (467-98-1)

Conditions	Yield
With ammonium chloride; zinc In ethanol

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) + benzene (71-43-2) + aqueous KOH → (8'Ξ)-4,5α;4',5'α-diepoxy-3,3'-dimethoxy-17,17'-dimethyl-7,8-didehydro-<7,8'>bimorphinanyl-6,6'-dione

Conditions	Yield

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) → 6β-acetoxy-4,5α-epoxy-3-methoxy-17-methyl-morphin-8(14)-ene (28379-40-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaBH4 / methanol 2: 3 h / 80 - 85 °C View Scheme

(4R,7aR,12bS)-9-methoxy-3-methyl-2,3,4,6-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (509-66-0) → dihydro-isocodeine (795-38-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaBH4 / methanol 2: H2, aq. HCl / PtO2 / 8 h / 760 Torr / Ambient temperature View Scheme

Upstream product

• 5140-31-8 (+)-14β-bromocodeinone 
• 32398-20-2 neopinone dimethyl acetal 
• 115-37-7 thebaine 
• 28406-17-9 14-bromo-4,5α-epoxy-3-methoxy-17-methyl-(14ξ)-morphin-7-en-6-one; hydrochloride 
• 102422-72-0 3a(R),9b(S)-dihydro-5-methoxy-9b-<2-(N-methylammonio)ethyl>phenanthro<4,4a,4b,5-bcd>furan-3(8H)-one trifluoroacetate 
• 1422-07-7 codeine hydrochloride 
• 76-57-3 codeine 
• 4599-09-1 14-bromo-4,5α-epoxy-3,6,6-trimethoxy-17-methyl-(14ξ)-morphin-7-ene 
• 916225-97-3 2-iodo-6-methoxy-3-(2,2-dimethoxyethyl)phenol 
• 1257051-27-6 benzyl 2-((5R,6R)-5-(tert-butyldimethylsilyloxy)-6-(3-(2,2-dimethoxyethyl)-2-iodo-6-methoxyphenoxy)cyclohex-1-enyl)ethylcarbamate 
• 1201905-44-3 benzyl N-[2-[(5aR,6R,9aS)-6-(tert-butyldimethylsilyloxy)-6,7-dihydro-1-(2,2-dimethoxyethyl)-4-methoxy-9a(5aH)-dibenzofuranyl]ethyl]carbamate 
• 1201905-45-4 C₃₂H₄₅N₃O₁₁SSi 
• 1201905-46-5 N-[2-[(5aR,6R,9aS)-6,7-dihydro-6-hydroxy-1-(2,2-dimethoxyethyl)-4-methoxy-9a(5aH)-dibenzofuranyl]ethyl]-N-methyl-2,4-dinitrobenzenesulfonamide 
• 1201905-48-7 N-[2-[(5aR,9aS)-6,7-dihydro-1-(2,2-dimethoxyethyl)-4-methoxy-6-oxo-9a(5aH)-dibenzofuranyl]ethyl]-N-methyl-2,4-dinitrobenzenesulfonamide 

Downstream Products

• 467-14-1 Neopin 
• 28379-40-0 Acetylisoneopin 
• 76-42-6 Oxycodone 

Relevant academic research and scientific papers

Compositions and Methods For Making Alkaloid Morphinans

Methods that may be used for the manufacture of a class of chemical compounds known as morphinans, including neopine, are provided. Compositions useful for the synthesis of morphinans, including neopine, are also provided.

Total Synthesis of (?)-Morphine

Asymmetric total synthesis of (?)-morphine has been accomplished in 18 steps from commercially available 7-methoxy-2-tetralone. Our synthesis features a simple transformation from a readily prepared chiral intermediate, construction of the E-ring by acid-mediated cyclization, and singlet oxygen-mediated manipulation of the C-ring. Transformation of the final stage involves construction of the morphinan skeleton by means of 1,6-addition of in situ generated secondary amine.

Total synthesis of (-)-morphine

We have developed an efficient total synthesis of (-)-morphine in 5% overall yield with the longest linear sequence consisting of 17 steps from 2-cyclohexen-1-one. The cyclohexenol unit was prepared by means of an enzymatic resolution and a Suzuki-Miyaura coupling as key steps. Construction of the morphinan core features an intramolecular aldol reaction and an intramolecular 1,6-addition. Furthermore, mild deprotection conditions to remove the 2,4-dinitrobenzenesulfonyl (DNs) group enabled the facile construction of the morphinan skeleton. We have also established an efficient synthetic route to a cyclohexenol unit containing an N-methyl-DNsamide moiety.

Combined biological and chemical catalysis in the preparation of oxycodone

The opioid oxycodone was produced from codeine, using a combination of chemical and biological catalysis. The use of novel functionalized ionic liquids permitted this reaction to be performed in a single solvent.