6-FLUORO-2-METHYLINDOLE

Synthesis of 6-fluoro-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.0 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 72 mg (4 mol percent) of cyclopentadienyidicarbonyliron (dimer) and 40 g of toluene were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (50 kgf/cm2), and the resulting mixture was reacted at a temperature of 120 C. for 5 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that 4-fluoro-2-nitrophenylacetone was completely disappeared and 0.64 g (yield 95.0percent) of 6-fluoro-2-methylindole was formed.Synthesis of 6-fluoro-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.0 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 178 mg (5 mol percent) of dichlorobis(triphenylphosphine)palladium, 0.48 g tin (II) chloride and 40 g of 1, 4-dioxane were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (20 kgf/cm2), and the resulting mixture was reacted at a temperature of 120 C. for 9 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that 4-fluoro-2-nitrophenylacetone was consumed by 98percent and 0.61 g (yield 91.0percent) of 6-fluoro-2-methylindole was formed.EXAMPLE 4 Synthesis of 6-fluoro-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.0 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 130 mg (4 mol percent) of trirutheniumdodecacarbonyl and 40 g of toluene were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (50 kgf/cm2), and the resulting mixture was reacted at a temperature of 180 C. for 4 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that the conversion rate of 4-fluoro-2-nitrophenylacetone was 91 percent and 0.53 g (yield 79.0percent) of 6-fluoro-2-methylindole was formed.3e (0.5mmol, 99 mg), zinc powder (3.0mmol, 196 mg), acetic acid (6.0mmol, 360 mg) put into the 25 ml in the reaction tube, and adding ethanol to 2 ml, 80 °C is stirred under the condition 4h. After cooling to room temperature the temperature of the reaction system by adding 25 ml water, add 25 ml ethyl acetate extraction, grass-roots takes has saturated salt water for washing, for NaEXAMPLE 7 Synthesis of 6-fluoro-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.0 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 102.5 mg (4 mol percent) of dichlorobis(triphenylphosphine)platinum, 0.48 g of tin(II) chloride and 30 g of 1, 4-dioxane were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (50 kgf/cm2), and the resulting mixture was reacted at a temperature of 120 C. for 8 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that the conversion rate of 4-fluoro-2-nitrophenylacetone was 92percent and 0.29 g (yield 44.0percent) of 6-fluoro-2-methylindole was formed.C: 6-Fluoro-2-methyl-lH-indoleTo a solution of l-(4-fluoro-2-nitrophenyl)-2-propanone (200mg 1.0 mmol) in acetone (3 mL) was added aqueous NHEXAMPLE 8 Synthesis of 6-fluoro-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.0 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 0.05 g of 5percent palladium supported on active carbon [manufactured by N.E. CHEMCAT CORPORATION (50percent water-containing product)], 0.48 g of tin (II) chloride, 0.20 g of triphenylphosphine and 40 g of 1, 4-dioxane were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (20 kgf/cm2), and the resulting mixture was reacted at a temperature of 120 C. for 4 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that the conversion rate of 4-fluoro-2-nitrophenylacetone was 33percent and 0.07 g (yield 10.0percent) of 6-fluoro-2-methylindole was formed.COMPARATIVE Synthesis of 6-fluoro-2-methylindole In a reaction flask the atmosphere inside of which was substituted by nitrogen, 1.00 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 10 g of 1-butanol and 0.05 g of 5percent palladium supported on active carbon [manufactured by N.E. CHEMCAT CORPORATION (50percent water-containing product)] were placed, hydrogen gas was supplied therein at ordinary pressure and 100 C., and the resulting mixture was reacted for 24 hours. After confirming the disappearance of 4-fluoro-2-nitrophenylacetone with liquid chromatography, the atmosphere was substituted by nitrogen, and the catalyst was filtered off through celite. The reaction solution was subjected to quantitative analysis with liquid chromatography, and as a result of it, it was confirmed that 0.53 g (yield 70percent) of 6-fluoro-2-methylindole was formed, and further 6-fluoro-1-hydroxy-2-methylindole and 6-fluoro-2-methylindoline were formed in a yield of 3percent and 25percent, respectively.COMPARATIVE Synthesis of 6-fluoro-2-methylindole In a reaction flask the atmosphere inside of which was substituted by nitrogen, 1.00 g (5.1 mmol) of 4-fluoro-2-nitrophenylacetone, 10 g of 2-ethoxyetanol and 0.05 g of 5percent palladium supported on active carbon [manufactured by N.E. CHEMCAT CORPORATION (50percent water-containing product)] were placed, hydrogen gas was supplied therein at ordinary pressure and 20 C., and the resulting mixture was reacted for 24 hours. After confirming the disappearance of 4-fluoro-2-nitrophenylacetone with liquid chromatography, the atmosphere was substituted by nitrogen, and the catalyst was filtered off through celite. The reaction solution was subjected to quantitative analysis with liquid chromatography, and as a result of it, it was confirmed that 0.13 g (yield 17percent) of 6-fluoro-2-methylindole was formed, and further 6-fluoro-1-hydroxy-2-methylindole and 6-fluoro-2-methylindoline were formed in a yield of 55percent and 11percent, respectively.Step 2a:6-Difluoro-2-methylindole 43 mg of copper(I) iodide are added to a solution of 1.7 g of 5-difluoro-2-prop-1-ynylphenylamine in 50 ml of DMF. The reaction medium is refluxed for one hour.After cooling, the reaction medium is filtered. The filtrate is concentrated under reduced pressure. The crude residue obtained is purified on a silica column, eluent: 90/10 cyclohexane/ethyl acetate, so as to give 1.1 g of 6-fluoro-2-methylindole, the characteristics of which are the following:Mass spectrometry: method ARetention time Tr (min)=0.89; [M+H]+: m/z 150

Molecular Weight:149.16
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:149.064077422
Monoisotopic Mass:149.064077422
Topological Polar Surface Area:15.8
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes