A common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, molecular formula is C7H7F2NO, 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. 22236-10-8.
Following General Procedure A, a solution of 4-difluoromethoxyaniline (0.50 g, 3.1 mmol) and (R)-3-(4-oxo-piperidin-1-yl)-butyronitrile (0.44 g, 2.6 mmol) in CH2Cl2 (10 mL), was treated with glacial AcOH (3 drops) and NaBH(OAc)3 (0.83 g, 3.9 mmol), stirring for 16 h at room temperature. Saturated aqueous NaHCO3 solution (15 mL) and 1N NaOH (2 mL) was added and the phases were separated and the aqueous extracted with CH2Cl2 (2¡Á15 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was then purified by flash column chromatography on silica gel (1:1 EtOAc/CH2Cl2) to afford (R)-3-[4-(4-difluoromethoxy-phenylamino)-piperidin-1-yl]-butyronitrile as a white solid (0.61 g, 76%). 1H NMR (CDCl3) delta 1.20 (d, 3H, J=6.6 Hz), 1.43 (m, 2H), 2.06 (br d, 2H), 2.36 (m, 3H), 2.52 (m, 1H), 2.82 (m, 2H), 3.07 (sex, 1H, J=7.2 Hz), 3.24 (m, 1H), 6.36 (t, 1H, J=75 Hz), 6.54 (d, 2H, J=9.0 Hz), 6.95 (d, 2H, J=9.0 Hz).
The synthetic route of 4-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.
Reference:
Patent; AnorMED Inc.; US2005/277668; (2005); A1;,
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