With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.399-51-9,6-Fluoro-1H-indole,as a common compound, the synthetic route is as follows.
To reactor A were charged diethoxymethane (DEM)(65 mE, 0.52 mol), water (50 mE) and formic acid (39 mE, 1.02 mol)). The mixture was heated at approx. 80 C. (reflux) for approx. 2 h and then cooled to approx. 20 C. To reactor B were charged 6-fluoroindole (50 g, 0.37 mol) and 80% acetic acid (66 mE, 1.17 mol). The suspension was cooled to 2-5 C. 40% Aq. dimethylamine (103 mE, 2.04 mol) was added drop- wise to reactor B keeping the temperature below approx. 15 C. The reaction mixture was stirred for approx. 20 mm and at the same time the temperature was adjusted to 2-4 C. The mixture from reactor A (DEM, water, formic acid, formaldehyde and ethanol at about 20 C.) was added drop-wise to reactor B while keeping the temperature at 2-8 C. The reaction mixture was stirred for additional 10 mm at 2-8 C. The reaction mixture was slowly warmed to approx.40 C. over a 1 h period. The reaction mixture was stirred at approx. 40C. for an additional 1 h. The reaction mixture was cooled to about 20 C. To reactor C was charged aq. NaOH (800 mE, 2.40 mol, 3 M) and the solution was cooled to about 10 C. The reaction mixture from reactor B was added dropwise to the NaOH solution in reactor C while keeping the temperature at 10-15C. (pH>14). The suspension was stirred for 40 mm at 5-20C. (pH>1 4). The product was collected by filtration and the filter-cake was washed twice with water (2×250 mE). The product was dried at approx. 60 C. under vacuum for 16 h to yield Compound (II) (67.6 g, 95%) with 98% UV purity in HPLC analysis., 399-51-9
As the paragraph descriping shows that 399-51-9 is playing an increasingly important role.
Reference：
Patent; H. Lundbeck A/S; JACOBSEN, Mikkel Fog; NIELSEN, Ole; (16 pag.)US2016/168089; (2016); A1;,
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