With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.162100-95-0,6-Fluoro-5-methyl-1H-indole,as a common compound, the synthetic route is as follows.
Diethylaluminum chloride 1M in hexane (25.1 mL, 25.1 mmol) was addeddropwise, at 000 and under N2-flow, to a solution of 6-fluoro-5-methyl-1 H-indole[CAS 162100-95-0] (2.5 g, 16.8 mmol) in CH2CI2 (135 mL). After 10 mm at 0C, a solution of 2-(2-(2-(benzyloxy)ethoxy)-4-fluorophenyl)acetyl chloride le (8.11 g, 25.1 mmol) in CH2CI2 (50 mL) was added dropwise at 0C over a period of 45 mm, while keeping the reaction temperature below 5C. The reaction was stirred at 0Cfor 2 h and at 10C for 2 h. The reaction mixture was cooled to 0C, and a solution of Rochelle salt [6100-16-9] (9.46 g, 33.5 mmol) in water (10 mL) was added dropwise. After addition, the reaction mixture was stirred at 0C for 10 minutes and then allowed to warm to room temperature. THE (150 mL) and Na2SO4 (40 g) were added, and the mixture was stirred for 18 h. The mixture was filtered overdicalite and washed with plenty of THE. The combined filtrates were evaporated under reduced pressure, and co-evaporated with toluene. The residue was crystallized from CH3CN (10 mL), filtered off, washed with CH3CN (2x), and dried under vacuum at 40C to provide a first fraction of 2-(2-(2-(benzyloxy)ethoxy)- 4-fluorophenyl)-1 -(6-fluoro-5-methyl-1 H-indol-3-yl)ethanone 7a (1 .86 g). Thefiltrate was evaporated under reduced pressure. The residue (7.7 g) was purified by flash chromatography (Stationary phase: Grace Reveleris silica 120 g, Mobile phase: heptane/EtOAc gradient 100/0 to 0/1 00). The fractions containing product were combined and left standing in an open recipient to allow evaporation of the solvent and crystallization of the product. The precipitate was isolated by filtration,washed 3x with heptane/EtOAc (1/1) and dried under vacuum at 40C to provide a second (1 .51 g) and third (0.75 g) fraction of intermediate 7a., 162100-95-0
162100-95-0 6-Fluoro-5-methyl-1H-indole 2774611, aindole-building-block compound, is more and more widely used in various fields.
Reference：
Patent; JANSSEN PHARMACEUTICALS, INC.; KATHOLIEKE UNIVERSITEIT LEUVEN; KESTELEYN, Bart Rudolf Romanie; RABOISSON, Pierre Jean-Marie Bernard; BONFANTI, Jean-Francois; JONCKERS, Tim Hugo Maria; BARDIOT, Dorothee Alice Marie-Eve; MARCHAND, Arnaud Didier M; (70 pag.)WO2017/46258; (2017); A1;,
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