Synthetic Route of 402-52-8,Some common heterocyclic compound, 402-52-8, name is 1-Methoxy-4-(trifluoromethyl)benzene, molecular formula is C8H7F3O, 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.
2-methoxy-5-(trifluoromethyl)benzoic acid (12-3). nBuLi (276 mL, 2.5 M, 0.69 mol, 1.1 equiv) and KOtBu (77 g, 0.69 mol, 1.1 equiv) were added to a THF solution (1 L) of crude 12-2 (110 g) at -78 0C. The reaction was stirred at -78 0C for 4 h. Dry CO2 was bubbled into the solution at -78 0C for 1 h. The reaction was allowed to warm to 25 0C over 0.5 h. NaOH (6N, 300 mL) and H2O were added to the resulting reaction mixture. The mixture was extracted with t-butylmethyl ether (400 mL x 2). The aqueous layer was acidified with HCl (6N) to pH 1 and extracted with EtOAc (300 mL x 4). The combined EtOAc extracts were concentrated and re- dissolved in CH2Cl2. The solution was dried (Na2SO4), filtered through a pad of Celite and concentrated. Flash chromatography on silica gel (1:1 PE/EtOAc) yielded 82 g of compound 12-3 (53% for 2 steps): 1H NMR (400 MHz, CDCl3) delta 8.45 (s, 1 H), 7.81 (d, J= 8.0 Hz5 1 H), 7.16 (d, J= 8.0 Hz5 1 H), 4.13 (s, 3 H); MS (ESI) m/z 221.0 (M+H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methoxy-4-(trifluoromethyl)benzene, its application will become more common.
Reference:
Patent; TETRAPHASE PHARMACEUTICALS, INC.; DENG, Yonghong; PLAMONDON, Louis; SUN, Cuixiang; XIAO, Xiao-Yi; ZHOU, Jingye; SUTCLIFFE, Joyce, A.; RONN, Magnus, P.; WO2011/25982; (2011); A2;,
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