These common heterocyclic compound, 22236-08-4, name is 3-(Difluoromethoxy)aniline, its 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. name: 3-(Difluoromethoxy)aniline
To a stirred solution of rn-difluoromethoxy aniline, 8.20 mL (65.5 rnmol) in anhydrous tetrahydrofuran (100 mE) at -78 C was added n-butyl lithium, 33.0 mE (65.5 mmol, 2 M in hexane) dropwise maintaining the reaction temperature below -65 C during the addition. The reaction mixture was stirred for 1 hour at -78 C before rac-phenyl 4-{[(allyloxy)carbonyl]amino}-N-cyano-3-(3,4- dichlorophenyl)-4,5-dihydro- 1 H-pyrazole- 1 -carboximidate (intermediate 5), 10,0 g (21.8 rnmol) inanhydrous tetrahydrofuran (600 mE) was added dropwise maintaining the reaction temperature below-65 C. The reaction mixture was stirred for 2 hours at -78 C before slowly pouring over saturated ammonium chloride solution (700 mE). The crude product was extracted into ethyl acetate (700 mL) and the organic layers were combined and washed with brine solution (350 mE). The collected organic phase was dried over magnesium sulfate, filtered and the solvent evaporated to yield an off-whitecrude solid. The crude solid was precipitated from a minimum volume of ethyl acetate and filtered, washing with diethyl ether to yield rac-allyl [1- {N?-cyano-N- [3- (difluoromethoxy)phenyl]carbamimidoyl} -3 -(3 ,4-dichlorophenyl)-4,5-dihydro- 1 H-pyrazol-4- yl]carbamate, 7.6 g (67%) as a white solid. LCMS (method 2): Rt = 1.78 min. MS (ESI): [M + H]+ = 523.2
The synthetic route of 3-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.
Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; STELLFELD, Timo; STRESEMANN, Carlo; HILLIG, Roman; KOeHR, Silke; STOeCKIGT, Detlef; WEISKE, Joerg; BARAK, Naomi; CHRIST, Clara; TER LAAK, Antonius; BADOCK, Volker; (77 pag.)WO2016/166185; (2016); A1;,
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