36127-17-0

Basic information

• Product Name: 2-CARBOMETHOXY-3-TROPINONE
• Synonyms: CARBOMETHOXY-TROPINONE;2-CARBOMETHOXY-3-TROPINONE;CARBMETHOXY-TROPINONE;Methyl 8-Methyl-3-oxobicyclo[3.2.1]octane-2-carboxylate;Methyl 8-Methyl-3-oxo-8-azabicyclo[3.2.1]octane-4-carboxylate;2-(Methoxycarbonyl)-3-tropanone;8-Azabicyclo[3.2.1]octane-2-carboxylicacid, 8-Methyl-3-oxo-, Methyl ester;8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-COOMe
• CAS NO: 36127-17-0
• Molecular Formula: C₁₀H₁₅NO₃
• Molecular Weight: 197.23
• EINECS: 237-344-8
• Product Categories: pharmacetical
• Mol File: 36127-17-0.mol
• Article Data: 6

Chemical Properties

• Melting Point: 104℃ (approx)
• Boiling Point: 294.108 °C at 760 mmHg
• Flash Point: 131.672 °C
• Appearance: /
• Density: 1.173±0.06 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 0.00166mmHg at 25°C
• Refractive Index: 1.502
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 10.89±0.20(Predicted)
• CAS DataBase Reference: 2-CARBOMETHOXY-3-TROPINONE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-CARBOMETHOXY-3-TROPINONE(36127-17-0)
• EPA Substance Registry System: 2-CARBOMETHOXY-3-TROPINONE(36127-17-0)

Safety Data

• Hazardous Substances Data: 36127-17-0(Hazardous Substances Data)

Usage

Description

2-Carbomethoxy-3-tropinone is an advanced intermediate in the biosynthesis of cocaine.

Uses

2-carbomethoxy-3-tropinone is an intermediate in the synthesis of cocaine isomers at the cocaine receptor.

InChI:InChI=1/C10H15NO3/c1-11-6-3-4-7(11)9(8(12)5-6)10(13)14-2/h6-7,9H,3-5H2,1-2H3

Synthetic route

tropinone (532-24-1) + carbonic acid dimethyl ester (616-38-6) → (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0)

Conditions	Yield
With methanol; sodium hydride In cyclohexane for 1.75h; Heating;	80%

3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester (100371-46-8) → (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) + tropinone (532-24-1)

Conditions	Yield
With phosphate buffer In water at 20℃; for 24h; pH=8.0; Decarboxylation; demethoxycarbonylation;	A 55% B 13%

1-methyl-pyrrolidine-diacetic acid-(2.5)-dimethyl ester → (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0)

Conditions	Yield
With 4-methylisopropylbenzene; sodium at 160 - 170℃;

butanedial (638-37-9) + methylamine (74-89-5) + dipotassium salt of acetone-α.α'-dicarboxylic acid monomethyl ester → (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0)

Conditions	Yield
With water; methylamine hydrochloride at -5℃;

tropinone-dicarboxylic acid-(2.4)-dimethyl ester → (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0)

Conditions	Yield
With hydrogenchloride
With potassium hydroxide

Lipase PS + 3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester (100371-46-8) → (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0)

Conditions	Yield
In toluene	48.5 mol %

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → S-(+)-allopseudoecgonine methyl ester (50373-09-6)

Conditions	Yield
With hydrogen; platinum(IV) oxide In ethanol under 2585.7 Torr; for 96h;	90%

N,N-phenylbistrifluoromethane-sulfonimide (37595-74-7) + (+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → (rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid 2-methyl ester

Conditions	Yield
Stage #1: (+/-)-2-(carbomethoxy)-3-tropinone With sodium hydride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at 0 - 20℃;	78%

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → C10H16(2)HNO3 (134753-23-4)

Conditions	Yield
With sodium borodeuteride In deuteromethanol

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → methyl (endo, endo)-3-hydroxy-8-methyl-8-azabicyclo<3.2.1>octan-2-carboxylate (46255-79-2)

Conditions	Yield
With sodium tetrahydroborate In methanol at -30℃; for 4h;

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) + sulfuric acid (7664-93-9) + lead cathode → (+-)-pseudoecgonine methyl ester + (+-)-ecgonine methyl ester

Conditions	Yield
bei der elektrolytischen Reduktion;

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) + sodium amalgam + acid → pseudotropine (135-97-7) + (+-)-ecgonine methyl ester + (+-)-pseudoecgonine methyl ester

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → (1S)-anhydroecgonine methyl ester (50373-10-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / H2 / PtO2 / ethanol / 96 h / 2585.7 Torr 2: DMAP, Et3N, TFAA / CH2Cl2 / 40 h / Ambient temperature View Scheme

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → methyl ecgonidine (50373-10-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / H2 / PtO2 / ethanol / 96 h / 2585.7 Torr 2: DMAP, Et3N, TFAA / CH2Cl2 / 40 h / Ambient temperature View Scheme

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → (+/-)-alloecgonine (79735-02-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / methanol / 4 h / -30 °C 2: 44 percent / H2O / Heating View Scheme

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → (1S,3S,5R)-3-Hydroxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester (46255-78-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaBH4 / methanol / 4 h / -30 °C 2: 44 percent / H2O / Heating 3: 82 percent / HCl / 16 h / 50 °C 4: 83 percent / K2CO3 View Scheme

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → (+/-)-alloecgonine methyl ester hydrochloride (79735-03-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4 / methanol / 4 h / -30 °C 2: 44 percent / H2O / Heating 3: 82 percent / HCl / 16 h / 50 °C View Scheme

(+/-)-2-(carbomethoxy)-3-tropinone (36127-17-0) → cocaine (21030-43-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / methanol / 4 h / -30 °C 2: 4-(dimethylamino)pyridine / CH2Cl2 View Scheme

Upstream product

• 638-37-9 butanedial 
• 78315-99-8 acetone-1,3-dicarboxylic acid mono-methyl ester 
• 593-51-1 methylamine hydrochloride 
• 532-24-1 tropinone 
• 616-38-6 carbonic acid dimethyl ester 
• 10521-08-1 pyran-2,4,6-trione 
• 100371-46-8 3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester 
• 74-89-5 methylamine 
• 77-92-9 citric acid 
• 1830-54-2 3-oxopentanedioic acid dimethyl ester 
• 532-24-1 tropinone 
• 17640-15-2 methyl cyanoformate 

Downstream Products

• 46255-79-2 methyl (endo, endo)-3-hydroxy-8-methyl-8-azabicyclo<3.2.1>octan-2-carboxylate 
• 7143-09-1 methyl (2-endo, 3-exo)-3-hydroxy-8-methyl-8-azabicyclo<3.2.1>octan-2-carboxylate 
• 135-97-7 pseudotropine 
• 43021-26-7 methyl 8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate 
• 21030-43-3 cocaine 

Relevant articles and documents

METHOD FOR THE PREPARATION OF N-MONOFLUOROALKYL TROPANES AND THEIR USE

The present invention relates to a method for the preparation of an N-monofluoroalkyl tropane, a method for the preparation of a trialkyltin tropane, a method for the preparation of an iodinated and/or radioiodinated tropane and the use of the N-monofluoroalkyl tropane as a precursor in the method for the preparation of the trialkyltin tropane and/or the iodinated and/or radioiodinated tropane.

Process for producing optically active tropinonemonocarboxylic acid derivative

An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

Stereoselective deprotonation of tropinone and reactions of tropinone lithium enolate

Tropinone (6) was deprotonated with lithium diisopropylamide and with chiral lithium amides (18-24) and the resulting enolates (two enantiomers) were treated with electrophiles.The aldol reaction with benzaldehyde and deuteration were both diastereoselective.The former yielded only one isomer (exo, anti) of the aldol 8a; the latter proceeded from the exo face.This selectivity permitted us to probe the deprotonation of tropinone with lithium amides; it was concluded that the reaction involves predominantly the exo axial protons.The reaction of tropinone enolate with ethyl chloroformate led, via a ring opening, to the cycloheptenone derivative 9.The reaction with methyl cyanoformate yielded, in the presence of silver acetate and acetic acid, the β-ketoester 8b; however, in the absence of these additives, and especially when 12-crown-4 was added to the enolate, a ring opening leading to the pyrrolidine derivative 10 occured instead.Deprotonation of tropinone with chiral amides proceeded with modest enantioselectivity.A synthesis of non-racemic anhydroecgonine via this strategy allowed establishing the absolute stereochemistry of deprotonation.