6-FLUOROINDOLE-3-CARBOXALDEHYDE

Yellow crystal

General procedure: Oxalyl chloride (0.3 mL) was added in a drop-wise manner to cooled (ice-bath) DMF (3 mL) under stirring. The mixture was then stirred at 0 °C for 1 h. A solution of the substituted indole (4 mmol) in DMF (1.5 mL) was then added to the reaction mixture in a dropwise manner. The resulting mixture was stirred at room temperature for 5 h. A 2 N solution of sodium hydroxide (2 mL) was then added, and the mixture was heated at 100 °C for 10 min. The mixture was then cooled and extracted with ethyl acetate (3 X 50 mL). The organic layers were combined and washed with sequentially water and brine. The organics were dried (NaPlace 40 ml DMF in a round bottom flaskSlowly add 6.89 ml of POCl3 (phosphorus oxychloride) under ice bath.After dropping, After stirring in an ice bath for 35 minutes, At a constant pressure dropping funnel was slowly added 5g6- fluoro indole in DMF, Stir at 35 °C for 40 min.The reaction solution gradually changed from colorless to red.TLC shows that after the reaction is completed, Add 100ml of 19.3mmol/L aqueous NaOH, Stir vigorously for 30 minutes at 80°C.Cool the reaction solutionAdd ethyl acetate extraction, 30ml each time, A total of three extractions.Organic layers merge, After drying over anhydrous sodium sulfate, Evaporated to drynessSilica gel column chromatography 4.5g Intermediate I-1 (white solid, yield75percent).General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol, 1.0 equiv), 37percent aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25percent aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g, 2 molpercent), and DMF (2 mL). The flask was fitted with a reflux condenser, and the mixture was stirred at 130 °C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL), and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane–EtOAc).General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N, N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 ° C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally, The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g, The product yield was 94percent.[6-FLUOROINDOLE-3-CARBOXALDEHYDE] (206.8 mg, 1.27 [MMOL), ] ammonium acetate (245.0 mg, 3.18 mmol), and nitroethane (0.271 mL, 5.08 mmol) were placed in a scintillation vial. Acetic acid (0.21 mL) was added and the vial was heated with a heat gun until a homogeneous solution developed. The reaction vessel was placed in a sonicating bath set on maximum. After 10 minutes, the reaction became heterogenous. The vial was heated as previously described. This cycle was repeated until homogeneity persisted. The reaction vessel was sonicated for 14 hours. The reaction contents were diluted with 10 mL [OF CH2CI2] and washed with 20 mL of [HZO.] The organic phase was passed through a plug of silica and concentrated to give 243 mg of [6-FLUORO-3- ( (E)-2-NITROPROPENYL)-IH-INDOLE] as a bright red powder (88% yield).A. 6-Fluoro-3-(2-nitropropenyl)-1H-indole was prepared by combining General procedure: To 3 mL of DMF was added phosphoryl chloride (2.04 g, 13.3 mmol) dropwise at 0 C. The mixture was stirred for half an hour, then a solution of 5-fluoroindole (1.5 g, 11.1 mmol) in 2 mL of DMF was added dropwize into the mixture. The resulting mixuture was heated to 25 C and reacted for 24 hours. The reaction mixture was quenched with 30 mL of water and neutralized with sodium carbonate solid to the pH=8-9. The mixture was filtered and the filter cake was dried in vacuo to give the title compound as a yellow solid (1.56 g, 86%). The compound was characterized by the following spectroscopic data:General procedure: (5.0 ml, 33.00 mmol) of anhydrous N, N-dimethylformamide was added to a round bottom flask under nitrogen.After cooling to 0 C, phosphorus oxychloride (6.0 ml, 33.00 mmol) was slowly added dropwise, and after returning to room temperature, Slowly add (1.00 g, 6.6 mmol) of a mixture of 5-chloroindole N, N-dimethylformamide, and react at room temperature for 3 h.Until the raw material disappears completely, pour the reaction solution into water, and adjust the pH with a saturated sodium carbonate solution (pH=8).Then, it was extracted with ethyl acetate, and the organic phase was collected, dried over anhydrous sodium sulfate and evaporated.Obtained crude product, purified by column chromatography ( petroleum ether: ethyl acetate = 2:1).A yellow solid 5-chloroindole-3-carbaldehyde (0.95 g, 80.2%) was obtained.

Molecular Weight:163.15
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:163.043341977
Monoisotopic Mass:163.043341977
Topological Polar Surface Area:32.9
Heavy Atom Count:12
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes