169674-57-1, The synthetic route of 169674-57-1 has been constantly updated, and we look forward to future research findings.
With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.169674-57-1,5-Chloro-6-fluoro-1H-indole,as a common compound, the synthetic route is as follows.
10 g (68.7 mmol) of 4-chloro-3-fluoro-phenylamine were dissolved in 38 ml dichloro-methane and treated with a solution of 6.82 g (72.1 mmol) of sodium bicarbonate in water (110 ml). At RT 8 ml (103 mmol) of methyl chloroformate were added dropwise over a period of 25 min (temperature rise from 22 to 28 C.). After stirring for 1.5 h at RT, the reaction mixture was diluted with dichloromethane (100 ml). After phase separation, the organic layer was washed with brine (45 ml), dried with magnesium sulfate, filtered and diluted with hexane (140 ml). The dichloromethane was then removed in vacuo and the resulting suspension filtered leading to 13 g (4-chloro-3-fluoro-phenyl)-carbamic acid methyl ester as a white powder (92%). MS (El) 203.1 (M)+.5.34 g (26.2 mmol) of (4-chloro-3-fluoro-phenyl)-carbamic acid methyl ester were dissolved in acetonitrile (50 ml) and treated with 6.49 g (28.85 mmol) of N-iodosuccinimide and 0.23 ml (2.62 mmol) of trifluoromethanesulfonic acid under nitrogen and stirred at RT for 3 hours. The reaction mixture was then poured into 50 ml of saturated sodium bicarbonate solution and extracted twice with ethyl acetate. The combined organic extracts were then washed with brine, dried with magnesium sulfate, filtered and concentrated in vacuo, leading to 8.2 g of (4-chloro-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester (95%) as a dark blue powder. MS (EI) 328.9 (M)+.153 mg (0.22 mmol) of Pd(PPh3)2Cl2 and 42 mg (0.22 mmol) of CuI were dissolved in 40 ml of triethylamine under argon and the mixture was heated to reflux for 20 min. The reaction mixture was then cooled to 0 C. and 7.2 g (21 mmol) of (4-chloro-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester were added. After 10 min stirring at RT, 3.45 ml (24.9 mmol) of ethynyltrimethylsilane were added dropwise (exothermic, temperature rise from 18 to 33 C.) and the reaction mixture was stirred for one hour at RT. The mixture was then poured into 180 ml of aqueous 1N HCl and ice and extracted with ethyl acetate. The organic extracts were then washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The remaining crude material (ca 21 mmol) was dissolved in THF (200 ml) and treated with 43.3 ml (43.3 mmol) of tetrabutylammonium fluoride (1M in THF) at RT. After 5 min stirring at RT, the reaction mixture was refluxed for one hour under argon. The reaction mixture was then cooled to RT and concentrated in vacuo. The resulting oil was treated with water (55 ml), stirred for 10 min and finally extracted with ethyl acetate. The combined organic layers were sequentially washed with 1M HCl (50 ml), saturated sodium bicarbonate (50 ml), brine (50 ml) and finally dried with magnesium sulfate, filtered and concentrated in vacuo. The remaining residue was suspended in hexane (200 ml) and-the mixture was heated to reflux, then cooled to 5 C. and the solid was collected by filtration leading to 3.15 g of 5-chloro-6-fluoro-1H-indole as a light brown solid (85%). MS (EI) 169.1 (M)+.35 ml of THF were cooled to -75 C. and 19.05 ml (30.5 mmol) of a 1.6M solution of n-butyllithium in hexane were added under argon. Then a solution of 2.35 g (13.7 mmol) of 5-chloro-6-fluoro-1H-indole in THF (9 ml) was added dropwise (temperature kept between -70 and -75 C.) over 15 min. After 5 additional min of stirring at this temperature a solution of 3.7 g of potassium tert-butylate in THF (15 ml) was added over period of 10 min (temperature kept between -70 and -75 C.). The resulting brown solution was then stirred for 2 hours at the same temperature and treated with a large excess of solid CO2. The temperature was then raised to 10 C. over a period of 75 min and water (30 ml) was added to the reaction mixture. After separation of the organic layer, the aqueous layer was extracted with ether and treated with concentrated HCl to adjust the pH to 1. The resulting suspension was then filtered and the solid was washed with water and dried in high vacuo. The remaining residue was suspended in 10 ml of hexane/ether 9:1 and stirred for 15 min, filtered off, washed with 5 ml of the same solvent mixture and was dried in high vacuo, leading to 2.2 g of 5-chloro-6-fluoro-1H-indole-7-carboxylic acid as a light brown solid (75%). MS: 212.2 (M-H)-
169674-57-1, The synthetic route of 169674-57-1 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; Faeh, Christoph; Kuehne, Holger; Luebbers, Thomas; Mattei, Patrizio; Maugeais, Cyrille; Pflieger, Philippe; US2007/185113; (2007); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles