Synthetic Route of 658-89-9,Some common heterocyclic compound, 658-89-9, name is 4-(Trifluoromethoxy)benzene-1,2-diamine, molecular formula is C7H7F3N2O, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a stirred solution of N-boc-O-methyl-L-threonine (1.99 g, 8.53 mmol) in acetonitrile (27 ml) at 0C was added N-methylmorpholine (1.3 ml, 12.0 mmol) followed by the dropwise addition of isobutyl chloroformate (1.3 ml, 10 mmol). The reaction mixture was stirred at 0C for 45 minutes. 4-(Trifluoromethoxy)benzene-1,2-diamine (1.64 g, 8.53 mmol) was dissolved in acetonitrile (14 mL) and cooled to 0C. To this was added the solution of the activated N-Boc-O-methyl-L-threonine via a dropping funnel fitted with a cotton wool plug. After the addition was complete the dropping funnel and cotton wool plug was rinsed with acetonitrile (10 mL) and was stirred at room temperature overnight. The reaction concentrated in vacuo, then diluted with EtOAc (80 mL) and citric acid (40 mL, 5% aqueous solution) was added. The organics were separated, washed with citric acid (40 mL, 5% aqueous solution), followed by brine (20 mL), dried over sodium sulphate and reduced in volume to afford an orange solid (3.69 g) which was used without further purification (mix of regioisomers). tert-Butyl ((1R,2R)-2-methoxy-1-(6-(trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)propyl)carbamate. A mixture of tert-butyl ((2S,3R)-1-((2-amino-4-(trifluoromethoxy)phenyl)amino)-3-methoxy-1-oxobutan-2-yl)carbamate and tert-butyl ((2S,3R)-1-((2-amino-5-(trifluoromethoxy)phenyl)amino)-3-methoxy-1-oxobutan-2-yl)carbamate (3.48 g, 8.54 mmol) was diluted with acetic acid (33 ml) and stirred at room temperature for 4.5 days. The reaction was quenched by slow addition of a K2CO3 solution (10% aqueous solution, 50 ml) and EtOAc (50 ml) was added. The organics were separated, combined and washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo to afford a dark brown gum which was purified by column chromatography (120g ISCO column, 0-30% EtOAc/heptane) to obtain 1.64 g (49%) of the title compound as a solid. This was taken on to next step without further purification. 1H NMR (400 MHz, DMSO-d6) delta 12.43 (br. s., 1H), 7.54 (br. s., 2H), 7.13 (br. s., 1H), 7.02 (d, J=7.81 Hz, 1H), 4.83 (dd, J=4.98, 8.10 Hz, 1H), 3.72-3.85 (m, 1H), 3.21 (s, 3H), 1.38 (s, 9H), 1.02 (d, J=6.25 Hz, 3H)
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(Trifluoromethoxy)benzene-1,2-diamine, its application will become more common.
Reference:
Article; Brown, Alan D.; Bagal, Sharan K.; Blackwell, Paul; Blakemore, David C.; Brown, Bruce; Bungay, Peter J.; Corless, Martin; Crawforth, James; Fengas, David; Fenwick, David R.; Gray, Victoria; Kemp, Mark; Klute, Wolfgang; Malet Sanz, Laia; Miller, Duncan; Murata, Yoshihisa; Payne, C. Elizabeth; Skerratt, Sarah; Stevens, Edward B.; Warmus, Joseph S.; Bioorganic and Medicinal Chemistry; vol. 27; 1; (2019); p. 230 – 239;,
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