40311-13-5

Basic information

• Product Name: 6-FLUORO-2-METHYLINDOLE
• Synonyms: 6-FLUORO-2-METHYLINDOLE;1H-Indole, 6-fluoro-2-Methyl-;6-Flioro-2methylindole
• CAS NO: 40311-13-5
• Molecular Formula: C₉H₈FN
• Molecular Weight: 149.1649232
• Mol File: 40311-13-5.mol
• Article Data: 8

Chemical Properties

• Melting Point: 100
• Boiling Point: 269℃
• Flash Point: 117℃
• Appearance: /
• Density: 1.219
• Vapor Pressure: 0.012mmHg at 25°C
• Refractive Index: 1.627
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 16.97±0.30(Predicted)
• CAS DataBase Reference: 6-FLUORO-2-METHYLINDOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 6-FLUORO-2-METHYLINDOLE(40311-13-5)
• EPA Substance Registry System: 6-FLUORO-2-METHYLINDOLE(40311-13-5)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 40311-13-5(Hazardous Substances Data)

Usage

InChI:InChI=1/C9H8FN/c1-6-4-7-2-3-8(10)5-9(7)11-6/h2-5,11H,1H3

Synthetic route

1-(4-fluoro-2-nitrophenyl)propan-2-one (39616-99-4) → 6-fluoro-2-methyl-1H-indole (40311-13-5)

Conditions	Yield
With [2,2]bipyridinyl; carbon monoxide; dodecacarbonyltriruthenium(0) In toluene Product distribution / selectivity;	97%
With carbon monoxide; cyclopentadienyl iron(II) dicarbonyl dimer In toluene at 120℃; for 9h; Product distribution / selectivity;	95%
With carbon monoxide; tin(ll) chloride; bis-triphenylphosphine-palladium(II) chloride In 1,4-dioxane at 120℃; for 9h; Product distribution / selectivity;	91%

1-(4-fluoro-2-nitrophenyl)propan-2-one (39616-99-4) + 1,10-Phenanthroline (66-71-7) → 6-fluoro-2-methyl-1H-indole (40311-13-5)

Conditions	Yield
dodecacarbonyltriruthenium(0) In toluene Product distribution / selectivity;	94%

1-(4-fluoro-2-nitrophenyl)propan-2-one (39616-99-4) → 6-fluoro-2-methyl-2,3-dihydro-1H-indole + 6-fluoro-2-methyl-1H-indole (40311-13-5) + 6-fluoro-1-hydroxy-2-methylindole

Conditions	Yield
With hydrogen; 5%-palladium/activated carbon In butan-1-ol at 100℃; for 24h; Product distribution / selectivity;	A 25% B 70% C 3%
With hydrogen; 5%-palladium/activated carbon In 2-ethoxy-ethanol at 20℃; for 24h; Product distribution / selectivity;	A 11% B 17% C 55%

5-fluoro-2-iodoaniline → 6-fluoro-2-methyl-1H-indole (40311-13-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride; triethylamine / -30 - 20 °C 2: copper(l) iodide / N,N-dimethyl-formamide / 1 h / Reflux View Scheme

5-fluoro-2-prop-1-ynylphenylamine (1383976-65-5) → 6-fluoro-2-methyl-1H-indole (40311-13-5)

Conditions	Yield
With copper(l) iodide In N,N-dimethyl-formamide for 1h; Reflux;	1.1 g

(E)-1-fluoro-4-(2-nitroprop-1-en-1-yl)benzene → 6-fluoro-2-methyl-1H-indole (40311-13-5)

Conditions	Yield
With 1,10-Phenanthroline; [(1,10-phenanthroline)Pd](tetrafluoroborate)2; carbon monoxide; triethylamine In acetonitrile at 150℃; under 15001.5 Torr; for 2.5h; Schlenk technique; Inert atmosphere;	57 %Spectr.

2-bromo-5-fluoronitrobenzene (446-09-3) → 6-fluoro-2-methyl-1H-indole (40311-13-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; palladium diacetate; triphenylphosphine / toluene / 5 h / 120 °C / Schlenk technique; Inert atmosphere 2: zinc; acetic acid / ethanol / 4 h / 70 °C / Inert atmosphere View Scheme

6-fluoro-2-methyl-1H-indole (40311-13-5) + acetophenone (98-86-2) → 2-methyl-6-fluoro-3-(1-phenylethenyl)-1H-indole (1621004-91-8)

Conditions	Yield
With 4-n-butyl-4-(3-sulfopropyl)thiomorpholinium 1,1-dioxide trifluoromethane sulfonate In neat (no solvent) at 60℃; for 0.25h; Ionic liquid; Green chemistry;	95%

6-fluoro-2-methyl-1H-indole (40311-13-5) + 2,2,2-trifluoroethyl(2,4,6-trimethylphenyl)iodonium trifluoromethanesulfonate → 6-fluoro-2-methyl-3-(2,2,2-trifluoroethyl)-1H-indole

Conditions	Yield
With 2,6-di-tert-butyl-pyridine In dichloromethane at 25℃; for 0.166667h; regioselective reaction;	94%

2-oxo-propionic acid ethyl ester (617-35-6) + 6-fluoro-2-methyl-1H-indole (40311-13-5) → ethyl 2-(6-fluoro-2-methyl-1H-indol-3-yl)acrylate

Conditions	Yield
With 3-(1,1-dioxido-4-(3-(3-(3-sulfopropyl)-1H-imidazol-3-ium-1-yl)propyl)thiomorpholino-4-ium)propane-1-sulfonate trifluoromethanesulfonate In acetic acid butyl ester at 80℃; for 0.5h; Green chemistry;	93%

3-bromo-6-fluoro-2-methyl indole (606092-05-1) + 6-fluoro-2-methyl-1H-indole (40311-13-5) + 3-chlorosuffonyl-1-(N,N-dimethylsulfamoyl)-3-chlorosulfonyl-1,2,4-triazole + tetrabutylammomium bromide (1643-19-2) → 3-[(3-bromo-6-fluoro-2-methyl-1H-indol-1-yl)sulfonyl]-N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide (348635-87-0)

Conditions	Yield
With sodium hydroxide In water; toluene	91.2%

6-fluoro-2-methyl-1H-indole (40311-13-5) → (S)-6-fluoro-2-methylindoline

Conditions	Yield
With hydrogenchloride; chloro(1,5-cyclooctadiene)rhodium(I) dimer; (S,R)-ZhaoPhos; hydrogen; acetic acid In dichloromethane at 25℃; under 30402 Torr; for 48h; Autoclave; enantioselective reaction;	90%

6-fluoro-2-methyl-1H-indole (40311-13-5) + 2,2-diphenylacetic acid (117-34-0) → C23H18FN

Conditions	Yield
With aluminium(III) triflate; Co(acac)3; hydrogen; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] at 130℃; under 22502.3 Torr; for 18h; Autoclave; Sealed tube;	88%

phenylacetic acid (103-82-2) + 6-fluoro-2-methyl-1H-indole (40311-13-5) → C17H16FN

Conditions	Yield
With aluminium(III) triflate; Co(acac)3; hydrogen; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] at 160℃; under 22502.3 Torr; for 18h; Autoclave; Sealed tube;	70%

6-fluoro-2-methyl-1H-indole (40311-13-5) + fullerene-C60 (99685-96-8, 161105-99-3, 161106-00-9, 111138-12-6, 133318-63-5, 134053-11-5, 134931-35-4, 134931-36-5, 139703-76-7, 145633-27-8, 175414-73-0, 175414-74-1, 175414-75-2, 175519-12-7, 175519-13-8, 175519-14-9, 175519-15-0, 136376-46-0, 144906-37-6, 144906-38-7, 151767-00-9, 152882-97-8, 152882-98-9, 152882-99-0, 153062-34-1, 154171-74-1, 154171-75-2, 154333-99-0, 154334-00-6, 154397-63-4, 154460-59-0, 199456-56-9, 108739-25-9, 120329-57-9, 120329-58-0) → C69H5FN2

Conditions	Yield
With trifluoroacetic acid; sodium nitrite In dimethyl sulfoxide; 1,2-dichloro-benzene at 25℃; for 1h; Sealed tube; regioselective reaction;	63%

6-fluoro-2-methyl-1H-indole (40311-13-5) + (2-nitroethenyl)benzene (102-96-5) → C17H15FN2O2

Conditions	Yield
With C66H64Ag2N8O4(2+)*2F6P(1-); palladium diacetate In isopropyl alcohol at 30℃; for 24h; Friedel-Crafts Alkylation; Inert atmosphere; Schlenk technique;	61%

6-fluoro-2-methyl-1H-indole (40311-13-5) → 3-bromo-6-fluoro-2-methyl indole (606092-05-1)

Conditions	Yield
With hydrogen bromide; dimethyl sulfoxide In water; toluene at 18 - 22℃; for 8 - 9h; Product distribution / selectivity;

6-fluoro-2-methyl-1H-indole (40311-13-5) + 3-bromo-6-fiuoro-2-methylindole → 3-bromo-6-fluoro-2-methyl indole (606092-05-1)

Conditions	Yield
With hydrogen bromide In water; dimethyl sulfoxide; toluene

6-fluoro-2-methyl-1H-indole (40311-13-5) → N-(2-((6-fluoro-2-methyl-1H-indol-3-yl)methyl)phenyl)benzenesulfonamide

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluoroacetic acid / 1,2-dichloro-ethane / 12 h / 50 °C 2: pyridine / dichloromethane / 12 h / 0 - 20 °C View Scheme

6-fluoro-2-methyl-1H-indole (40311-13-5) → 6-fluoro-2-methyl-1'-(phenylsulfonyl)spiro[indole-3,2'-indoline]

Conditions	Yield
Multi-step reaction with 3 steps 1: trifluoroacetic acid / 1,2-dichloro-ethane / 12 h / 50 °C 2: pyridine / dichloromethane / 12 h / 0 - 20 °C 3: [bis(acetoxy)iodo]benzene / 0.5 h / 20 °C View Scheme

2-Aminobenzyl alcohol (5344-90-1) + 6-fluoro-2-methyl-1H-indole (40311-13-5) → C16H15FN2

Conditions	Yield
With trifluoroacetic acid In 1,2-dichloro-ethane at 50℃; for 12h;

Upstream product

• 39616-99-4 1-(4-fluoro-2-nitrophenyl)propan-2-one 
• 66-71-7 1,10-Phenanthroline 
• 255724-71-1 5-fluoro-2-iodoaniline 
• 1383976-65-5 5-fluoro-2-prop-1-ynylphenylamine 
• 446-09-3 2-bromo-5-fluoronitrobenzene 

Downstream Products

• 348635-87-0 amisulbrom 
• 1621004-91-8 2-methyl-6-fluoro-3-(1-phenylethenyl)-1H-indole 

Relevant articles and documents

Method for preparing indole and derivatives thereof

The invention discloses a method for preparing indole and derivatives of indole. The method for preparing indole and the derivatives of indole is characterized by comprising the following two steps that (1) a catalyst, a ligand and alkali are added in a reaction tube, under the protection of nitrogen, beta-hydroxy ketone or ester is reacted with a mixed solution of o-nitro aryl halides for 3 to 8h in an oil bath pan at the temperature of 90 to 120 DEG C, and then cooled to room temperature after reaction, and extracted, washed, dried and subjected to chromatography to obtain a product of o-nitro alpha-aryl ketone or ester; (2) o-nitro alpha-aryl ketone or ester obtained in the step (1), a reducing agent system and a solvent are added to the reaction tube, and reacted for 3 to 8h at the temperature of 60 to 100 DEG C, and then extracted, washed, dried and subjected to chromatography after being reacted to obtain a target product of indole and the derivatives of indole. Reaction raw materials, the catalyst, the ligand, the alkali and the solvent used in the invention are all industrial commodities, and simple and readily available, wide in sources, cheap in price, and further very stable in performances, and with no need for special storage conditions; in addition, the method for preparing indole and the derivatives of indole disclosed by the invention has the characteristics of low cost, high yield, simple process, less pollution and the like.

Synthesis of Indoles by Palladium-Catalyzed Reductive Cyclization of β-Nitrostyrenes with Carbon Monoxide as the Reductant

An efficient catalytic cyclization of β-nitrostyrenes to indoles was developed. The reaction was applied to the synthesis of 3-arylindoles and 2-alkylindoles. Given that in the latter case the starting β-nitrostyrenes can be easily obtained by a Henry reaction, the present method allows indoles to be obtained in a two-step sequence starting from cheap reactants.

PIPERIDINYLHYDROXYETHYLPIPERIDINES AS MODULATORS OF CHEMOKINE RECEPTORS

The present invention relates to a compound of the formula (I), or a pharmaceutically acceptable salt thereof, wherein R1-R8 and X, m, and n are defined. Compounds and compositions of the present invention are useful the treatment of atherosclerosis.