41340-36-7

Basic information

• Product Name: 7-Ethyl tryptophol
• Synonyms: 3-(7-ETHYLINDOLE)ETHANOL;2-(7-Ethylindol-3-yl)ethanol;2-(3a-ethyl-3aH-indol-3-yl)ethanol;7-Ethyl-3-indoleethanol;7-ETHYLTRYPTOPHOL;7-ETHYL-1H-INDOLE-3-ETHANOL;7-ETHYL-3-(2-HYDROXYETHYL)INDOLE;2-(7-ETHYL-1H-INDOL-3-YL)-ETHANOL
• CAS NO: 41340-36-7
• Molecular Formula: C₁₂H₁₅NO
• Molecular Weight: 189.25
• EINECS: 431-020-1
• Product Categories: INTERMEDIATESOFETODOLAC;Indole derivatives;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 41340-36-7.mol
• Article Data: 11

Chemical Properties

• Melting Point: 44-45°C
• Boiling Point: 377.814 °C at 760 mmHg
• Flash Point: 182.296 °C
• Appearance: /
• Density: 1.147 g/cm³
• Vapor Pressure: 5.41E-05mmHg at 25°C
• Refractive Index: 1.564
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.98±0.10(Predicted)
• CAS DataBase Reference: 7-Ethyl tryptophol(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Ethyl tryptophol(41340-36-7)
• EPA Substance Registry System: 7-Ethyl tryptophol(41340-36-7)

Safety Data

• Hazard Codes: Xn;N,N,Xn
• Statements: 22-48/22-51/53
• Safety Statements: 2-36/37/39-61
• RIDADR: 3077
• RTECS: NL8512200
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 41340-36-7(Hazardous Substances Data)

Usage

Chemical Properties

Pale Beige Solid

Uses

Different sources of media describe the Uses of 41340-36-7 differently. You can refer to the following data:
1. 7-Ethyltryptophol (Etodolac EP Impurity H) is a key intermediate in the preparation of the non-steroidal anti-inflammatory drug Etodolac.
2. Key intermediate in the preparation of the non-steroidal anti-inflammatory drug Etodolac.

InChI:InChI=1/C12H15NO/c1-2-12-7-4-3-5-11(12)13-9-10(12)6-8-14/h3-5,7,9,14H,2,6,8H2,1H3

Synthetic route

2,3-dihydro-2H-furan (1191-99-7) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7)

Conditions	Yield
With sodium hydrogencarbonate In water at 130℃; for 0.833333h; Reagent/catalyst; Solvent; Concentration; Fischer Indole Synthesis; Microwave irradiation;	85%
With sulfuric acid In N,N-dimethyl acetamide; water at 80℃; Reagent/catalyst; Solvent;	69%
Stage #1: 2,3-dihydro-2H-furan; 2-ethylphenylhydrazine hydrochloride With hydrogenchloride; sodium hydroxide In water; ethylene glycol at 115℃; for 0.00666667h; Fischer Indole Synthesis; Flow reactor; Stage #2: With sulfuric acid at 115℃; for 0.0616667h; Concentration; Temperature; Time; Pressure; Fischer Indole Synthesis; Flow reactor;	50%

2,3-dihydro-2H-furan (1191-99-7) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + C12H18N2O (1226954-31-9)

Conditions	Yield
With sodium hydrogencarbonate In water at 130℃; for 0.25h; Solvent; Reagent/catalyst; Concentration; Fischer Indole Synthesis; Microwave irradiation;	A 84% B 6%
With sulfuric acid In tert-butyl methyl ether; water at 150℃; for 0.0166667h; Solvent; Reagent/catalyst; Fischer Indole Synthesis; Microwave irradiation;	A 25% B 56%

ethyl (3-hydroxy-7-ethyl-2-oxindol-3-yl)-acetate → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7)

Conditions	Yield
With borane-THF In tetrahydrofuran at 20℃;	78%

2,3-dihydro-2H-furan (1191-99-7) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + C28H36N2O3 (1268685-97-7)

Conditions	Yield
With sulfuric acid In water at 130℃; for 0.0833333h; Solvent; Fischer Indole Synthesis; Microwave irradiation;	A 78% B 10%

2,3-dihydro-2H-furan (1191-99-7) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + C28H36N2O3 (1268685-97-7) + C12H18N2O (1226954-31-9)

Conditions	Yield
With sulfuric acid In tetrahydrofuran; water at 130℃; for 0.0833333h; Fischer Indole Synthesis; Microwave irradiation;	A 78% B 6% C 7%

4-hydroxybutyraldehyde (25714-71-0) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7)

Conditions	Yield
With ethylene glycol In water Microwave irradiation;	78%
Stage #1: 4-hydroxybutyraldehyde; 2-ethylphenylhydrazine hydrochloride In water; ethylene glycol at 115℃; for 0.00555556h; Stage #2: With sulfuric acid In water; ethylene glycol for 0.0666667h;

2-ethoxytetrahydrofuran (13436-46-9) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7)

Conditions	Yield
In ethanol for 12h; Heating;	43%

1,8-diethyl-1-methyl-1,3,4,9-tetrahydropyrano-<3,4-b>indole → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7)

Conditions	Yield
With hydrogenchloride In methanol; water at 85℃; Product distribution; Rate constant; Thermodynamic data; Ea, ΔS<*>, mechanism of etodolac degradation in aqueous solutionsat various temperatures (75-905 deg C), time and pH, effect of pH and temperature, catalytic effect of buffer system;

2,3-dihydro-7-ethyl-1H-indole-3-ethanol (114737-75-6) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 7-ethyl-5-hydroxytryptophol (114720-06-8)

Conditions	Yield
With potassiuim nitrosodisulfonate 1.) pH 7 buffer, Me2CO, 10 min, 2.) room temperature, overnight; Yield given. Multistep reaction;

etodolac (41340-25-4) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 7-ethyl-2-(1-methyl-1-propenyl)-1H-indole-3-ethanol + 7-ethyl-2-(1-methylenepropyl)-1H-indole-3-ethanol + 1,8-diethyl-1-methyl-1,3,4,9-tetrahydropyrano-<3,4-b>indole

Conditions	Yield
With hydrogenchloride In methanol; water at 85℃; for 18h; Product distribution; Rate constant; Thermodynamic data; Ea, ΔS<*>, mechanism of etodolac degradation in aqueous solutionsat various temperatures (75-905 deg C), time and pH, effect of pH and temperature, catalytic effect of buffer system;

7-ethylisatin (79183-65-6) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / pyridine; acetic acid / ethanol / Heating 2: 78 percent / BH3*THF / tetrahydrofuran / 20 °C View Scheme

C12H15NO (1421708-58-8) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 2-(3-indole)-ethanol (526-55-6) + 4-ethyltryptophol (41340-32-3)

Conditions	Yield
With hydrogenchloride In methanol; water at 150℃; for 0.166667h;

4-hydroxybutyraldehyde (25714-71-0) + 2-ethylphenylhydrazine hydrochloride (19398-06-2, 58711-02-7) + ethylene glycol (107-21-1) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 7-ethyltryptophol + C12H14N2O

Conditions	Yield
In water at 115℃; for 0.566667h; Inert atmosphere;

C12H18N2O (1226954-31-9) → 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 7-ethyltryptophol + C12H14N2O

Conditions	Yield
With sulfuric acid In water

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + methyl propanoyl acetate (30414-53-0) → methyl 1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)-indole-1-acetate

Conditions	Yield
With chloro-trimethyl-silane In methanol at 20℃; for 22h; Reagent/catalyst; Temperature;	99.9%
With sulfuric acid In methanol at 0 - 30℃; Reagent/catalyst; Pictet-Spengler Synthesis;	98%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + (E)-(3,3-dimethoxypent-1-en-1-yl)benzene → (R, E)-1,8-diethyl-1-styryl-1,3,4,9-tetrahydropyrano[3,4-b]indole

Conditions	Yield
With 2,3,4,5-tetrabromo-6-(((1R,2R)-2-(3-(3,4-dinitrophenyl)thioureido)cyclohexyl)carbamoyl)benzoic acid In toluene at -30℃; for 24h; Pictet-Spengler Synthesis; Molecular sieve; Inert atmosphere; enantioselective reaction;	96%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 8-(phenylethynyl)-1-naphthaldehyde → C31H27NO2

Conditions	Yield
With C27H38AuN2(1+)*C2F6NO4S2(1-) In 1,2-dichloro-ethane at 20℃; for 0.5h; Inert atmosphere; Schlenk technique; regioselective reaction;	95%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 3-oxopentanedioic acid dimethyl ester (1830-54-2) → (8-ethyl-1-methoxycarbonylmethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid methyl ester (200880-24-6)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 5h; Heating;	82%

epoxybutene (930-22-3) + 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) → 2-(2-(7-ethyl-1H-indol-3-yl)ethoxy)but-3-en-1-ol (1616561-97-7)

Conditions	Yield
With bis(η3-allyl-μ-chloropalladium(II)); triethyl borane; triphenylphosphine In tetrahydrofuran; dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	80%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + benzaldehyde dimethyl acetal (1125-88-8) → 8-ethyl-1-phenyl-1,3,4,9-tetrahydropyrano[3,4-b]indole + benzaldehyde (100-52-7)

Conditions	Yield
With camphor-10-sulfonic acid In chloroform for 16h; Reagent/catalyst; Solvent; Pictet-Spengler Synthesis; Schlenk technique; Inert atmosphere;	A 77% B 19 %Spectr.

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + bromoacetic acid methyl ester (96-32-2) → C15H19NO3

Conditions	Yield
With disodium hydrogenphosphate; [4,4′-di-tert-butyl-2,2′-bipyridine]bis[5-methyl-2-(4-methyl-2pyridinyl)phenyl]iridium(III) hexafluorophosphate In 1,2-dichloro-ethane at 20℃; for 20h; Inert atmosphere; Irradiation; regioselective reaction;	75%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + N-methoxy-N-(phenylsulfonyl)benzenesulfonamide → N-[2-(7-ethyl-1H-indol-3-yl)ethyl]-N-methoxybenzenesulfonamide

Conditions	Yield
With caesium carbonate In acetonitrile at 20℃; for 12h;	71%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + ethyl propanoylacetate (4949-44-4) → (RS)-etodolac ethyl ester (200880-23-5)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 5h; Heating;	67%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + (Z)-3-Methoxy-pent-2-enoic acid (1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl ester (351339-82-7) → ((R)-1,8-Diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid (1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl ester + ((S)-1,8-Diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid (1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl ester (351339-83-8)

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane for 2h;	A n/a B 60%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 4-chloro-3,3-dimethoxy-butylic acid ethyl ester (6567-42-6) → (1-chloromethyl-8-ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid ethyl ester (591752-24-8)

Conditions	Yield
With boron trifluoride diethyl etherate In 1,2-dichloro-ethane	58.6%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) → 2,3-dihydro-7-ethyl-1H-indole-3-ethanol (114737-75-6)

Conditions	Yield
With sodium tetrahydroborate In trifluoroacetic acid for 1h;	48%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 2-methyl-3-buten-2-ol (115-18-4) → (E)‐2‐(7‐ethyl‐2‐(3‐methyl‐1‐butenyl)‐3‐indolyl)ethan‐1‐ol

Conditions	Yield
With Nafion at 120℃; for 24h; Sealed tube; Inert atmosphere; Ionic liquid; regioselective reaction;	47%

2,3-dihydro-2H-furan (1191-99-7) + 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) → C28H36N2O3 (1268685-97-7)

Conditions	Yield
With hydrogenchloride In methanol; water at 130℃; for 0.00416667h;	43%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + (2R)-1,2-di(propionyloxy)pentan-3-one (241803-47-4) → (1S,1'R)-1,8-diethyl-1-(1',2'-dipropionyloxy)ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole (241803-51-0) + (1R,1'R)-1,8-diethyl-1-(1',2'-dipropionyloxy)ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole (241803-50-9)

Conditions	Yield
With boron trifluoride diethyl etherate In tetrahydrofuran at 45 - 50℃; for 60h; Cyclization;	A 20.9% B 41.3%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + (2R)-1,2-di(acetyloxy)pentan-3-one (241803-46-3) → (1S,1'R)-1,8-diethyl-1-(1',2'-diacetyloxy)ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole (241803-49-6) + (1R,1'R)-1,8-diethyl-1-(1',2'-diacetyloxy)ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole (241803-48-5)

Conditions	Yield
With boron trifluoride diethyl etherate In toluene at 25℃; for 72h; Cyclization;	A 12.5% B 35.2%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + 3-methoxypent-2-enedioic acid dimethyl ester (20414-58-8, 100009-70-9) → (8-ethyl-1-methoxycarbonylmethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid methyl ester (200880-24-6)

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 12h;	25.7%

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + p-toluenesulfonyl chloride (98-59-9) → C26H27NO5S2 + 7-ethyl-3-(2-iodoethyl)-1H-indole

Conditions	Yield
Stage #1: 7-ethyl-2-(1H-indol-3-yl)ethan-1-ol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran at 20℃; for 16h; Inert atmosphere;	A 14% B n/a

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + ethyl butyroyl acetate (3249-68-1) → (8-ethyl-1-propyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid (57816-83-8)

Conditions	Yield
(i) TsOH, benzene, (ii) aq. NaOH, EtOH; Multistep reaction;

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol (41340-36-7) + ethyl propanoylacetate (4949-44-4) → etodolac (41340-25-4)

Conditions	Yield
(i) TsOH, benzene, (ii) aq. NaOH, EtOH; Multistep reaction;

Upstream product

• 115066-03-0 1,8-diethyl-1-methyl-1,3,4,9-tetrahydropyrano-<3,4-b>indole 
• 41340-25-4 etodolac 
• 13436-46-9 2-ethoxytetrahydrofuran 
• 19398-06-2 2-ethylphenylhydrazine hydrochloride 
• 25714-71-0 4-hydroxybutyraldehyde 
• 1226954-31-9 C₁₂H₁₈N₂O 
• 107-21-1 ethylene glycol 
• 1191-99-7 2,3-dihydro-2H-furan 
• 79183-65-6 7-ethylisatin 
• 114737-75-6 2,3-dihydro-7-ethyl-1H-indole-3-ethanol 
• 1421708-58-8 C₁₂H₁₅NO 
• 96-49-1 [1,3]-dioxolan-2-one 
• 22867-74-9 7-ethyl-1H-indole 

Downstream Products

• 57816-83-8 (8-ethyl-1-propyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid 
• 122188-02-7 methyl 1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)-indole-1-acetate 
• 41340-25-4 etodolac 
• 100-52-7 benzaldehyde 
• 101901-06-8 6-hydroxyetodolac 
• 114737-75-6 2,3-dihydro-7-ethyl-1H-indole-3-ethanol 

Relevant articles and documents

Preparation method of 7-ethyl chrotol

The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of 7-ethyl chromone, which comprises the following steps: reacting 7-ethyl indole serving as a raw material with ethylene carbonate under the action of alkali to synthesize 7-ethyl chromone; the hydroxyethyl ethylene carbonate reagent product introduced in the method is carbon dioxide, the method is clean and environmentally friendly, post-treatment is convenient, dangerous chemical reagents are not used, the reaction is milder, economical and environmentally friendly, the yield is high, and the method is suitable for industrial production.

On the Fischer indole synthesis of 7-ethyltryptophol - Mechanistic and process intensification studies under continuous flow conditions

7-Ethyltryptophol, a key intermediate in the synthesis of the anti-inflammatory agent etodolac, was produced by Fischer indole synthesis of 2-ethylphenylhydrazine and 2,3-dihydrofuran under continuous flow conditions. The reaction generates several undesired byproducts and therefore product yields could not be improved above 40-50%. The mechanism of this transformation was studied in detail and the structure of the byproducts carefully elucidated. Despite the only moderate product yield, the synthesis of 7-ethyltryptophol by this protocol remains interesting compared to alternative methods and starts from inexpensive reagents. The developed process is executed in an environmentally benign solvent (methanol) and, importantly, the majority of byproducts can be removed from the 7-ethyltryptophol product by a straightforward extraction process.

A continuous kilogram-scale process for the manufacture of 7-ethyltryptophol

An expeditious and multikilogram-scale process for the synthesis of 7-ethyltryptophol via a continuous flow reactor from 2-ethylphenylhydrazine and 4-hydroxybutyraldehyde in higher and high yield was described. The main steps in this synthesis involved not only the generation of the hydrazone intermediate in situ but also the catalysis of the subsequent [3 + 3] sigmatropic rearrangement in the tandem loop reactor. Decomposition of the intermediate hydrazone was found to be a key factor resulting in low yield.