71042-72-3

Usage

InChI:InChI=1/C13H16O2/c1-3-15-13(14)12-8-7-9(2)10-5-4-6-11(10)12/h7-8H,3-6H2,1-2H3

Synthetic route

1-pyrrolidinocyclopent-1-ene (7148-07-4) + (2E,4E)-ethyl hexa-2,4-dienoate (2396-84-1) → ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3)

Conditions	Yield
Stage #1: 1-pyrrolidinocyclopent-1-ene; (2E,4E)-ethyl hexa-2,4-dienoate In 5,5-dimethyl-1,3-cyclohexadiene Reflux; Stage #2: With sulfur at 250℃; for 2h;	58%
With 2.) S 1.) xylene, reflux, 18h, 2.) 230 deg C, 30 min; Yield given. Multistep reaction;

1-pyrrolidinocyclopent-1-ene (7148-07-4) + (2E,4E)-ethyl hexa-2,4-dienoate (2396-84-1) → ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) + 7-Methyl-2,3,7,7a-tetrahydro-1H-indene-4-carboxylic acid ethyl ester (71042-73-4)

Conditions	Yield
In xylene for 18h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → 4-(7-Methylindan)carboxylic acid (71042-74-5)

Conditions	Yield
With potassium hydroxide In ethanol Heating;	95%

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → ethyl 6-bromo-7-methyl-2,3-dihydro-1H-indene-4-carboxylate

Conditions	Yield
With bromine; nitric acid; silver nitrate; acetic acid In water at 20℃;	80%

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → 4-(Chloromethanoyl)-7-methylindan (71042-75-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / aq. KOH / ethanol / Heating 2: 97 percent / thionyl chloride / 1 h / Heating View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (7-methyl-indan-4-yl)-[2]naphthyl ketone (78064-87-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / aq. KOH / ethanol / Heating 2: 97 percent / thionyl chloride / 1 h / Heating 3: AlCl3 / CH2Cl2 / 1 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 95 percent / aq. KOH / ethanol / Heating 2: 97 percent / thionyl chloride / 1 h / Heating 3: 1.) Mg, cuprous iodide / 1.) THF, 45 deg C, 15 min, 2.) 45 deg C, 0.5 h View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (7-methyl-indan-4-yl)-[1]naphthyl ketone (63665-87-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / aq. KOH / ethanol / Heating 2: 97 percent / thionyl chloride / 1 h / Heating 3: AlCl3 / CH2Cl2 / 1 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 95 percent / aq. KOH / ethanol / Heating 2: 97 percent / thionyl chloride / 1 h / Heating 3: 1.) Mg, cuprous iodide / 1.) THF, 45 deg C, 15 min, 2.) 45 deg C, 0.5h View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → 6-bromo-7-methyl-2,3-dihydro-1H-indene-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → C11H10BrClO

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Inert atmosphere View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (6-bromo-7-methyl-2,3-dihydro-1H-indene-4-yl)(4-methoxyphenyl)methanone

Conditions	Yield
Multi-step reaction with 4 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Inert atmosphere 4: aluminum (III) chloride / dichloromethane / 2 h / 0 - 20 °C View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → 5-bromo-7-(4-methoxybenzyl)-4-methyl-2,3-dihydro-1H-indene

Conditions

Yield

Multi-step reaction with 5 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Inert atmosphere 4: aluminum (III) chloride / dichloromethane / 2 h / 0 - 20 °C 5: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 0 - 20 °C / Inert atmosphere View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (2R,3R,4R,5S,6S)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-(7-(4-methoxybenzyl)-4-methyl-2,3-dihydro-1H-indene-5-yl)tetrahydro-2H-pyran

Conditions

Yield

Multi-step reaction with 7 steps 1.1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Inert atmosphere 4.1: aluminum (III) chloride / dichloromethane / 2 h / 0 - 20 °C 5.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 0 - 20 °C / Inert atmosphere 6.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -78 °C / Inert atmosphere 6.2: 2 h / -78 °C / Inert atmosphere 7.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 1 h / -78 - -60 °C / Inert atmosphere View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-(7-(4-methoxybenzyl)-4-methyl-2,3-dihydro-1H-indene-5-yl)tetrahydro-2H-pyran-3,4,5-triol

Conditions

Yield

Multi-step reaction with 8 steps 1.1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Inert atmosphere 4.1: aluminum (III) chloride / dichloromethane / 2 h / 0 - 20 °C 5.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 0 - 20 °C / Inert atmosphere 6.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -78 °C / Inert atmosphere 6.2: 2 h / -78 °C / Inert atmosphere 7.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 1 h / -78 - -60 °C / Inert atmosphere 8.1: palladium on carbon; hydrogen / tetrahydrofuran; methanol / 16 h View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (6-bromo-7-methyl-2,3-dihydro-1H-indene-4-yl)methanol

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → 5-bromo-7-(bromomethyl)-4-methyl-2,3-dihydro-1H-indene

Conditions	Yield
Multi-step reaction with 4 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4: phosphorus tribromide / toluene / 2 h / 0 - 20 °C / Inert atmosphere View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → 5-bromo-4-methyl-7-(4-methylbenzyl)-2,3-dihydro-1H-indene

Conditions

Yield

Multi-step reaction with 5 steps 1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4: phosphorus tribromide / toluene / 2 h / 0 - 20 °C / Inert atmosphere 5: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0) / water; acetone / 4 h / 20 °C View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → (2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-(4-methyl-7-(4-methylbenzyl)-2,3-dihydro-1H-indene-5-yl)tetrahydro-2H-pyran-3,4,5-triol

Conditions

Yield

Multi-step reaction with 7 steps 1.1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3.1: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4.1: phosphorus tribromide / toluene / 2 h / 0 - 20 °C / Inert atmosphere 5.1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0) / water; acetone / 4 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -78 °C / Inert atmosphere 6.2: 2 h / -78 °C / Inert atmosphere 6.3: 2 h / -78 °C 7.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 1 h / -78 - -50 °C / Inert atmosphere View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → C25H32O6

Conditions

Yield

Multi-step reaction with 6 steps 1.1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3.1: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4.1: phosphorus tribromide / toluene / 2 h / 0 - 20 °C / Inert atmosphere 5.1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0) / water; acetone / 4 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -78 °C / Inert atmosphere 6.2: 2 h / -78 °C / Inert atmosphere 6.3: 2 h / -78 °C View Scheme

ethyl 7-methyl-2,3-dihydro-1H-indene-4-carboxylate (71042-72-3) → C52H54O7

Conditions

Yield

Multi-step reaction with 6 steps 1.1: bromine; silver nitrate; acetic acid; nitric acid / water / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Inert atmosphere 4.1: aluminum (III) chloride / dichloromethane / 2 h / 0 - 20 °C 5.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 0 - 20 °C / Inert atmosphere 6.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -78 °C / Inert atmosphere 6.2: 2 h / -78 °C / Inert atmosphere View Scheme

Upstream product

• 7148-07-4 1-pyrrolidinocyclopent-1-ene 
• 2396-84-1 (2E,4E)-ethyl hexa-2,4-dienoate 

Downstream Products

• 71042-74-5 4-(7-Methylindan)carboxylic acid 
• 71042-75-6 4-(Chloromethanoyl)-7-methylindan 
• 63665-87-2 (7-methyl-indan-4-yl)-[1]naphthyl ketone 

Relevant academic research and scientific papers

C-GLUCOSIDE DERIVATIVE CONTAINING FUSED PHENYL RING OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PROCESS FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

The present disclosure relates to C-glycoside derivatives having a fused phenyl ring or pharmaceutical acceptable salts thereof, a method for preparing the same, a pharmaceutical composition comprising the same, a use thereof and a method for dual inhibition of SGLT1 and SGLT2 using the same. A novel compound of the present disclosure has a dual inhibitory activity against SGLT1 and SGLT2, thus being valuably used as a diabetes therapeutic agent.

Improved Synthesis of 3-Methylcholanthrene

An improved synthesis of 7-methylindan-4-yl 1-naphthyl ketone (3), an important precursor of 3-methylcholanthrene (1), has been developed.The key intermediates for 3, 4-cyano-7-methylindan (2a) and 4-(ethoxycarbonyl)-7-methylindan (2b), were conveniently prepared in high yields by reaction of 1-(1-pyrrolidino)cyclopentene (6) with sorbonitrile (5a) or ethyl sorbate (5b), followed by aromatization with sulfur. 1-Naphthylmagnesium bromide (4b) in the presence of cuprous iodide reacted cleanly with 4-(chloromethanoyl)-7-methylindan (12) to give 3.The Friedel-Crafts acylation of naphthalene with 12 afforded 84percent of 3 and 16percent of β isomer 13.Alternatively, 3 was prepared in 75percent yield by condensation of Grignard reagent 4b with 2a in THF.Thermal annelation of 3 afforded 1 in 41.5percent yield.