519-09-5

Basic information

• Product Name: BENZOYLECGONINE
• Synonyms: BENZOYLECGONINE;1alphaH,5alphaH-Tropane-2beta-carboxylic acid, 3beta-hydroxy-, benzoate (ester);3-(Benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid;8-Azabicyclo[3.2.1]octane-2-carboxylic acid, 3-(benzoyloxy)-8-methyl;8-Azabicyclo[3.2.1]octane-2-carboxylic acid, 3-(benzoyloxy)-8-methyl-, [1R-(exo,exo)]-;Benzoylecogonine;Ecgonine benzoate;o-Benzoyl-(-)-ecgonine
• CAS NO: 519-09-5
• Molecular Formula: C₁₆H₁₉NO₄
• Molecular Weight: 289.33
• EINECS: 208-263-5
• Product Categories: Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;AlkaloidsAlphabetic;BA - BHDrugs of Abuse;Drugs of Abuse;EcgoninenForensic and Veterinary Standards;Neat Compounds;B;Chemical Structure;Drugs&Metabolites;Solutions;Aromatics
• Mol File: 519-09-5.mol
• Article Data: 12

Chemical Properties

• Melting Point: 1950C (dec)
• Boiling Point: 431.49°C (rough estimate)
• Flash Point: 11 °C
• Appearance: Crystalline Solid
• Density: 1.1267 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: 2-8°C
• PKA: pKa 11.80 (Uncertain)
• CAS DataBase Reference: BENZOYLECGONINE(CAS DataBase Reference)
• NIST Chemistry Reference: BENZOYLECGONINE(519-09-5)
• EPA Substance Registry System: BENZOYLECGONINE(519-09-5)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25-25
• Safety Statements: 16-36/37-45-7
• RIDADR: UN 1230 3/PG 2
• WGK Germany: 1
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 519-09-5(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Uses

A metabolite of Cocaine. Controlled substance

Definition

ChEBI: A benzoate ester metabolite of cocaine formed by hydrolysis of the methyl ester group, catalysed by carboxylesterases.

InChI:InChI=1/C16H19NO4/c1-17-11-7-8-12(17)14(15(18)19)13(9-11)21-16(20)10-5-3-2-4-6-10/h2-6,11-14H,7-9H2,1H3,(H,18,19)/t11-,12+,13-,14+/m0/s1

Synthetic route

RTI-128 (155748-84-8) → benzylecgonine (519-09-5)

Conditions	Yield
With sodium nitrite In acetic anhydride; acetic acid 1.) 0 deg C, 16 h, 2.) room temperature, 8 h;	93%

(-)-cocaine hydrochloride (53-21-4) → benzylecgonine (519-09-5)

Conditions	Yield
With ammonia; water	86%
With dipotassium hydrogenphosphate; potassium dihydrogenphosphate In tetrahydrofuran; water at 80℃; for 3h;	83%
With sodium hydroxide for 12h; Heating; Yield given;

Cocaine (50-36-2) → benzylecgonine (519-09-5)

Conditions	Yield
With water for 24h; Reflux;	84%
With human carboxylesterase 1b, recombinant In aq. phosphate buffer at 37℃; for 1h; pH=7.4; Enzymatic reaction;
With water In 1,4-dioxane at 130℃; for 2h; Microwave irradiation;

benzoic acid anhydride (93-97-0) + ecgonine (481-37-8) → benzylecgonine (519-09-5)

Conditions	Yield
With acetone
With water at 100℃;

Cocaine (50-36-2) → methanol (67-56-1) + benzoic acid (65-85-0) + ecgonine (481-37-8) + methyl ecgonine (7143-09-1) + benzylecgonine (519-09-5)

Conditions	Yield
With hydrogenchloride In water at 70 - 90℃; Product distribution; Rate constant; Thermodynamic data; also in plasma and with other reagents ; ΔHa, ΔS(excit.), Arrhenius parameters;

Cocaine (50-36-2) → methyl ecgonine (7143-09-1) + benzylecgonine (519-09-5)

Conditions	Yield
at 37℃; Rate constant; various pH from 6.9 to 10.4; I=0.1 M;

water (7732-18-5) + benzoic acid anhydride (93-97-0) + ecgonine (481-37-8) → benzylecgonine (519-09-5)

Conditions	Yield
at 100℃;
at 100℃;

water (7732-18-5) + Cocaine (50-36-2) → benzylecgonine (519-09-5)

l-cocaine → benzylecgonine (519-09-5)

Conditions	Yield
With water

Cocaine (50-36-2) → methylecgonine benzoate + benzylecgonine (519-09-5)

Conditions	Yield
cocE-pIX Enzyme kinetics; Enzymatic reaction;
cocE-pIII Enzyme kinetics; Enzymatic reaction;
cocE Enzyme kinetics; Enzymatic reaction;

anhydroecgonine hydrochloride (74242-55-0) → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 13 steps 1: 93 percent / H2 / Pd/C / methanol / 6.5 h / 3102.9 Torr / Ambient temperature 2: 1.) (COCl)2, DMF, 2.) N-hydroxy-2-thiopyridone / 1.) CH2ClCH2Cl, room temperature, 12 h, 2.) CH2ClCH2Cl, room temperature, 1.5 h, 3.) CH2Cl2, irradiation, 0 deg C, 2 h 3: toluene / 24 h / Heating 4: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 5: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 6: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 7: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 8: 80 percent / 0.67 h / 105 - 110 °C 9: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 10: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 11: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 12: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 13: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 13 steps 1: 93 percent / H2 / Pd/C / methanol / 6.5 h / 3102.9 Torr / Ambient temperature 2: 1.) (COCl)2, DMF, 2.) N-hydroxy-2-thiopyridone / 1.) CH2ClCH2Cl, room temperature, 12 h, 2.) CH2ClCH2Cl, room temperature, 1.5 h, 3.) CH2Cl2, irradiation, 0 deg C, 2 h 3: toluene / 24 h / Heating 4: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 5: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 6: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 7: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 8: 80 percent / 0.67 h / 105 - 110 °C 9: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 10: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 11: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 12: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 13: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 13 steps 1: 93 percent / H2 / Pd/C / methanol / 6.5 h / 3102.9 Torr / Ambient temperature 2: 1.) (COCl)2, DMF, 2.) N-hydroxy-2-thiopyridone / 1.) CH2ClCH2Cl, room temperature, 12 h, 2.) CH2ClCH2Cl, room temperature, 1.5 h, 3.) CH2Cl2, irradiation, 0 deg C, 2 h 3: NaIO4 / H2O / 2 h / Ambient temperature 4: 57 percent / 75 °C / 0.08 - 0.1 Torr 5: 1.) 1-chloroethyl chloroformate, 3.) Et3N / 1.) toluene, reflux, 16 h, 2.) MeOH, reflux, 16 h, 3.) room temperature, 14 h 6: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 7: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 8: 80 percent / 0.67 h / 105 - 110 °C 9: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 10: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 11: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 12: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 13: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,5S)-8-Methyl-2-phenylselanyl-8-aza-bicyclo[3.2.1]octane → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 11 steps 1: toluene / 24 h / Heating 2: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 3: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 4: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 5: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 6: 80 percent / 0.67 h / 105 - 110 °C 7: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 8: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 9: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 10: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 11: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 11 steps 1: toluene / 24 h / Heating 2: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 3: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 4: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 5: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 6: 80 percent / 0.67 h / 105 - 110 °C 7: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 8: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 9: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 10: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 11: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 11 steps 1: NaIO4 / H2O / 2 h / Ambient temperature 2: 57 percent / 75 °C / 0.08 - 0.1 Torr 3: 1.) 1-chloroethyl chloroformate, 3.) Et3N / 1.) toluene, reflux, 16 h, 2.) MeOH, reflux, 16 h, 3.) room temperature, 14 h 4: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 5: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 6: 80 percent / 0.67 h / 105 - 110 °C 7: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 8: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 9: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 10: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 11: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

C14H19NOSe (208038-05-5) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 10 steps 1: 57 percent / 75 °C / 0.08 - 0.1 Torr 2: 1.) 1-chloroethyl chloroformate, 3.) Et3N / 1.) toluene, reflux, 16 h, 2.) MeOH, reflux, 16 h, 3.) room temperature, 14 h 3: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 4: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 5: 80 percent / 0.67 h / 105 - 110 °C 6: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 7: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 8: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 9: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 10: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,5R)-8-Methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid; hydrochloride → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 12 steps 1: 1.) (COCl)2, DMF, 2.) N-hydroxy-2-thiopyridone / 1.) CH2ClCH2Cl, room temperature, 12 h, 2.) CH2ClCH2Cl, room temperature, 1.5 h, 3.) CH2Cl2, irradiation, 0 deg C, 2 h 2: toluene / 24 h / Heating 3: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 4: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 5: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 6: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 7: 80 percent / 0.67 h / 105 - 110 °C 8: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 9: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 10: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 11: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 12: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 12 steps 1: 1.) (COCl)2, DMF, 2.) N-hydroxy-2-thiopyridone / 1.) CH2ClCH2Cl, room temperature, 12 h, 2.) CH2ClCH2Cl, room temperature, 1.5 h, 3.) CH2Cl2, irradiation, 0 deg C, 2 h 2: toluene / 24 h / Heating 3: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 4: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 5: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 6: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 7: 80 percent / 0.67 h / 105 - 110 °C 8: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 9: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 10: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 11: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 12: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 12 steps 1: 1.) (COCl)2, DMF, 2.) N-hydroxy-2-thiopyridone / 1.) CH2ClCH2Cl, room temperature, 12 h, 2.) CH2ClCH2Cl, room temperature, 1.5 h, 3.) CH2Cl2, irradiation, 0 deg C, 2 h 2: NaIO4 / H2O / 2 h / Ambient temperature 3: 57 percent / 75 °C / 0.08 - 0.1 Torr 4: 1.) 1-chloroethyl chloroformate, 3.) Et3N / 1.) toluene, reflux, 16 h, 2.) MeOH, reflux, 16 h, 3.) room temperature, 14 h 5: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 6: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 7: 80 percent / 0.67 h / 105 - 110 °C 8: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 9: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 10: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 11: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 12: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

tropidine (208037-81-4) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 1.) 1-chloroethyl chloroformate, 3.) Et3N / 1.) toluene, reflux, 16 h, 2.) MeOH, reflux, 16 h, 3.) room temperature, 14 h 2: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 3: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 4: 80 percent / 0.67 h / 105 - 110 °C 5: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 6: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 7: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 8: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 9: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-2-one (208037-76-7) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 11 steps 1: 96 percent / H2 / Pd/C / methanol / 5 h 2: 88 percent / methanol / 2 h / Ambient temperature 3: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 4: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 5: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 6: 80 percent / 0.67 h / 105 - 110 °C 7: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 8: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 9: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 10: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 11: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,5S)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester (208037-78-9) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 2: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 3: 80 percent / 0.67 h / 105 - 110 °C 4: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 5: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 6: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 7: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 8: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,5S)-8-(tert-butyloxycarbonyl)-8-azabicyclo[3.2.1]-2-octanone (208037-77-8) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 10 steps 1: 88 percent / methanol / 2 h / Ambient temperature 2: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 3: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 4: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 5: 80 percent / 0.67 h / 105 - 110 °C 6: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 7: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 8: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 9: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 10: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(2R,5S)-5-[1'-(2'-methoxycarbonyl)ethyl]proline methyl ester (208037-73-4) → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 13 steps 1: 93 percent / Et3N / methanol / 14 h / Ambient temperature 2: 85 percent / KHMDS / tetrahydrofuran / 6 h / -78 °C 3: 87 percent / NaI / pyridine / 7.5 h 4: 88 percent / methanol / 2 h / Ambient temperature 5: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 6: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 7: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 8: 80 percent / 0.67 h / 105 - 110 °C 9: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 10: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 11: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 12: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 13: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 14 steps 1: 96 percent / K2CO3 / acetonitrile / 14 h / Ambient temperature 2: 90 percent / KHMDS / tetrahydrofuran / 1 h / -78 °C 3: 90 percent / NaI / pyridine / 8 h / Heating 4: 96 percent / H2 / Pd/C / methanol / 5 h 5: 88 percent / methanol / 2 h / Ambient temperature 6: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 7: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 8: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 9: 80 percent / 0.67 h / 105 - 110 °C 10: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 11: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 12: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 13: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 14: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(2R,5S)-5-(2-Carboxy-ethyl)-pyrrolidine-2-carboxylic acid tert-butyl ester (208037-72-3) → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 14 steps 1: 95 percent / AcCl / 14 h / Heating 2: 93 percent / Et3N / methanol / 14 h / Ambient temperature 3: 85 percent / KHMDS / tetrahydrofuran / 6 h / -78 °C 4: 87 percent / NaI / pyridine / 7.5 h 5: 88 percent / methanol / 2 h / Ambient temperature 6: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 7: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 8: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 9: 80 percent / 0.67 h / 105 - 110 °C 10: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 11: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 12: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 13: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 14: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme
Multi-step reaction with 15 steps 1: 95 percent / AcCl / 14 h / Heating 2: 96 percent / K2CO3 / acetonitrile / 14 h / Ambient temperature 3: 90 percent / KHMDS / tetrahydrofuran / 1 h / -78 °C 4: 90 percent / NaI / pyridine / 8 h / Heating 5: 96 percent / H2 / Pd/C / methanol / 5 h 6: 88 percent / methanol / 2 h / Ambient temperature 7: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 8: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 9: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 10: 80 percent / 0.67 h / 105 - 110 °C 11: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 12: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 13: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 14: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 15: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,2R,3S,5S)-2-cyano-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (208037-85-8) → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 2: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 3: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 4: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 5: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate (208037-75-6) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 12 steps 1: 90 percent / NaI / pyridine / 8 h / Heating 2: 96 percent / H2 / Pd/C / methanol / 5 h 3: 88 percent / methanol / 2 h / Ambient temperature 4: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 5: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 6: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 7: 80 percent / 0.67 h / 105 - 110 °C 8: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 9: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 10: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 11: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 12: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

Benzoic acid (1R,2R,3S,5S)-2-carbamoyl-8-aza-bicyclo[3.2.1]oct-3-yl ester (208037-88-1) → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 2: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,2R,3S,5S)-2-Carbamoyl-3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (208037-86-9) → benzylecgonine (519-09-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 2: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 3: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 4: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,2S,5S)-2-Phenylselanyl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (208037-82-5) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 2: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 3: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 4: 80 percent / 0.67 h / 105 - 110 °C 5: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 6: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 7: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 8: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 9: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,2R,5S)-2-Phenylselanyl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (208038-13-5) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 2: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 3: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 4: 80 percent / 0.67 h / 105 - 110 °C 5: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 6: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 7: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 8: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 9: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,2S,5S)-2-Phenylselanyl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 1-chloro-ethyl ester (208037-92-7) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 10 steps 1: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 2: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 3: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 4: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 5: 80 percent / 0.67 h / 105 - 110 °C 6: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 7: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 8: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 9: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 10: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,2R,5S)-2-Phenylselanyl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 1-chloro-ethyl ester → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 10 steps 1: 2.) Et3N / 1.) MeOH, reflux, 2 h, 2.) MeOH, room temperature, 15 h 2: 91 percent / NaIO4 / tetrahydrofuran; H2O / 2 h / Ambient temperature 3: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 4: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 5: 80 percent / 0.67 h / 105 - 110 °C 6: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 7: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 8: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 9: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 10: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

(1R,5S)-2-Hydroxy-8-aza-bicyclo[3.2.1]oct-2-ene-3,8-dicarboxylic acid 8-tert-butyl ester 3-methyl ester (208037-90-5) → benzylecgonine (519-09-5)

Conditions

Yield

Multi-step reaction with 11 steps 1: 87 percent / NaI / pyridine / 7.5 h 2: 88 percent / methanol / 2 h / Ambient temperature 3: 70 percent / NaH / toluene / 1.) room temperature, 30 min, 2.) reflux, 5 h 4: 78 percent / Na2CO3*H2O / tetrahydrofuran; H2O / 16 h 5: 96 percent / aq. NaOH / ethanol / 1.) 0 deg C, 1 h, 2.) room temperature, 1.5 h 6: 80 percent / 0.67 h / 105 - 110 °C 7: 94 percent / Na2CO3, aq. H2O2 / H2O / 24 h / Ambient temperature 8: 96 percent / DMAP / CH2Cl2 / 12 h / Ambient temperature 9: 90 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 10: 75 percent / NaBH3CN / acetonitrile / 1 h / Ambient temperature 11: 93 percent / NaNO2 / acetic acid; acetic anhydride / 1.) 0 deg C, 16 h, 2.) room temperature, 8 h View Scheme

diazomethane (186581-53-3, 908094-01-9) + benzylecgonine (519-09-5) → Cocaine (50-36-2)

Conditions	Yield
In dichloromethane	95%

benzylecgonine (519-09-5) + trimethyleneglycol (504-63-2) → 1-hydroxy-3-propyl benzoylecgonine

Conditions	Yield
Stage #1: benzylecgonine With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; Stage #2: trimethyleneglycol In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃;	95%
Stage #1: benzylecgonine With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 24h; Stage #2: trimethyleneglycol In dichloromethane
Stage #1: benzylecgonine With 1,1'-carbonyldiimidazole In dichloromethane for 22h; Stage #2: trimethyleneglycol In dichloromethane at 20℃; for 6h;

propan-1-ol (71-23-8) + benzylecgonine (519-09-5) → RTI 13 (64091-46-9)

Conditions	Yield
With hydrogenchloride at 0℃; for 48h;	83%

ethyl iodide (75-03-6) + benzylecgonine (519-09-5) → cocaethylene (529-38-4)

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine In dichloromethane for 72h; Ambient temperature;	72%
With ethanol at 100℃; im Rohr;

benzyl 6-bromohexanoate (78277-26-6) + benzylecgonine (519-09-5) → (1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-benzyloxycarbonyl-pentyl ester (173443-26-0)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 80℃;	72%

6-amino-hexanoic acid benzyl ester toluene-4-sulfonic acid (5514-99-8) + benzylecgonine (519-09-5) → (1R,2R,3S,5S)-2-((6-(benzyloxy)-6-oxohexyl)carbamoyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate

Conditions	Yield
Stage #1: 6-amino-hexanoic acid benzyl ester toluene-4-sulfonic acid; benzylecgonine With dmap In dichloromethane for 1.5h; Inert atmosphere; Cooling with ice; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane for 96h; Inert atmosphere;	71%

t-butyl (RS)-phenylalaninate (16367-71-8) + benzylecgonine (519-09-5) → Benzoic acid (1R,2R,3S,5S)-2-(1-tert-butoxycarbonyl-2-phenyl-ethylcarbamoyl)-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl ester

Conditions	Yield
With benzotriazol-1-yl-oxy-tris-pyrrolidinophosphonium; triethylamine In dichloromethane for 12h; Ambient temperature;	65%

ethanol (64-17-5) + benzylecgonine (519-09-5) → cocaethylene (529-38-4)

Conditions	Yield
Stage #1: benzylecgonine With oxalyl dichloride at 20℃; for 0.333333h; Stage #2: ethanol at 20℃; for 12h;	60%
With hydrogenchloride
With hydrogenchloride at 0℃; for 48h;

diisopropyl-carbodiimide (693-13-0) + benzylecgonine (519-09-5) → Benzoic acid (1R,2R,3S,5S)-2-(N,N'-diisopropyl-carbamimidoyloxycarbonyl)-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl ester + Benzoic acid (1R,2R,3S,5S)-2-(1-tert-butoxycarbonyl-2-phenyl-ethylcarbamoyl)-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl ester

Conditions	Yield
With t-butyl (RS)-phenylalaninate In dichloromethane Ambient temperature;	A 58% B 15%

t-butyl (RS)-phenylalaninate (16367-71-8) + benzylecgonine (519-09-5) → (S)-N-benzoylphenylalanine tert-butyl ester (109309-90-2)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	34%

benzylecgonine (519-09-5) → 3β-(benzoyloxy)-2β-(hydroxymethyl)-8-methyl-8-azabicyclo<3.2.1>octane (137718-56-0)

Conditions	Yield
With B2H6-THF In tetrahydrofuran at 0 - 20℃; for 3h;	31%

methanol (67-56-1) + benzylecgonine (519-09-5) → Cocaine (50-36-2)

Conditions	Yield
With hydrogenchloride

Isobutyl iodide (513-38-2) + benzylecgonine (519-09-5) → (1R)-3exo-benzoyloxy-tropane-2exo-carboxylic acid isobutyl ester

Conditions	Yield
With 2-methyl-propan-1-ol at 95℃; im Rohr;

1-iodo-propane (107-08-4) + benzylecgonine (519-09-5) → RTI 13 (64091-46-9)

Conditions	Yield
With propan-1-ol at 95℃; im Rohr;

ethylene dibromide (106-93-4) + benzylecgonine (519-09-5) → 3-benzoyloxy-tropane-2-carboxylic acid-(2-bromo-ethyl ester)

Conditions	Yield
With ethanol at 95℃; im Rohr; O-benzoyl-l-ecgonine-<β-bromo-ethyl ester>;

benzylecgonine (519-09-5) + methyl iodide (74-88-4) → Cocaine (50-36-2)

Conditions	Yield
With methanol at 100℃; im Rohr;
With methanol; sodium methylate at 100℃; im Rohr;

benzylecgonine (519-09-5) → (+)-pseudoecgonine (481-38-9)

Conditions	Yield
With potassium hydroxide
With potassium hydroxide

benzylecgonine (519-09-5) → ecgonine (481-37-8)

Conditions	Yield
With hydrogenchloride

benzylecgonine (519-09-5) → 2-β-benzamido-3β-tropanol

Conditions	Yield
With thionyl chloride Behandeln des Reaktionsprodukts mit NaN3 in H2O, Erwaermen mit wss. HCl und anschliessendes Behandeln mit wss. NaOH;

benzylecgonine (519-09-5) → benzoylnorecgonine (41889-45-6)

Conditions	Yield
With potassium permanganate; sodium carbonate

2-(4-nitrophenyl)ethanol (100-27-6) + benzylecgonine (519-09-5) → 3β-(benzoyloxy)-8-methyl-8-azabicyclo<3.2.1>octane-2β-carboxylic acid (p-nitrophenyl)ethyl ester (137819-59-1)

Conditions	Yield
With 1,1'-carbonyldiimidazole 1.) CH2Cl2, RT, 6 h, 2.) acetone, reflux, 3 h; Yield given. Multistep reaction;

2-phenylethanol (60-12-8) + benzylecgonine (519-09-5) → RTI 53 (137718-50-4)

Conditions	Yield
With 1,1'-carbonyldiimidazole 1.) CH2Cl2, RT, 6 h, 2.) acetone, reflux, 3 h; Yield given. Multistep reaction;

methylamine (74-89-5) + benzylecgonine (519-09-5) → 3β-(benzoyloxy)-8-methyl-8-azabicyclo<3.2.1>octane-2β-carboxylic acid N-methylamide (137819-57-9)

Conditions	Yield
With 1,1'-carbonyldiimidazole 1.) CH2Cl2, RT, 1 h, 2.) CH2Cl2, 3 h; Yield given. Multistep reaction;

benzyl alcohol (100-51-6) + benzylecgonine (519-09-5) → RTI 52 (137718-48-0)

Conditions	Yield
With 1,1'-carbonyldiimidazole 1.) CH2Cl2, RT, 6 h, 2.) acetone, reflux, 3 h; Yield given. Multistep reaction;

benzylecgonine (519-09-5) → benzoylecgonine acid chloride (61194-36-3)

Conditions	Yield
With thionyl chloride
With thionyl chloride at 0℃; for 4h;
With oxalyl dichloride In dichloromethane for 1h; Ambient temperature;
With oxalyl dichloride for 0.25h; Substitution;

Upstream product

• 93-97-0 benzoic acid anhydride 
• 481-37-8 ecgonine 
• 50-36-2 Cocaine 
• 53-21-4 (-)-cocaine hydrochloride 
• 155748-84-8 RTI-128 
• 7732-18-5 water 
• 74242-55-0 anhydroecgonine hydrochloride 
• 208038-05-5 C₁₄H₁₉NOSe 
• 208037-81-4 tropidine 
• 208037-76-7 (1R,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-2-one 
• 208037-78-9 (1R,5S)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester 
• 208037-77-8 (1R,5S)-8-(tert-butyloxycarbonyl)-8-azabicyclo[3.2.1]-2-octanone 
• 208037-73-4 (2R,5S)-5-[1'-(2'-methoxycarbonyl)ethyl]proline methyl ester 
• 208037-72-3 (2R,5S)-5-(2-Carboxy-ethyl)-pyrrolidine-2-carboxylic acid tert-butyl ester 

Downstream Products

• 50-36-2 Cocaine 
• 529-38-4 cocaethylene 
• 64091-46-9 RTI 13 
• 481-37-8 ecgonine 
• 41889-45-6 benzoylnorecgonine 
• 137718-56-0 3β-(benzoyloxy)-2β-(hydroxymethyl)-8-methyl-8-azabicyclo<3.2.1>octane 
• 61194-36-3 benzoylecgonine acid chloride 
• 65-85-0 benzoic acid 
• 109309-90-2 (S)-N-benzoylphenylalanine tert-butyl ester 
• 110-15-6 succinic acid 
• 481-38-9 (+)-pseudoecgonine 
• 137819-58-0 3β-(benzoyloxy)-2β-(acetoxymethyl)-8-methyl-8-azabicyclo<3.2.1>octane 
• 137819-55-7 RTI 14 
• 137819-56-8 RTI 15 

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