反应详情

温度

60 °C

{2-Methyl-6-[3-(quinolin-2-ylmethoxy)-propoxymethyl]-phenoxy}-acetonitrile (333 mg, 0.89 mmol, EXAMPLE 6a) is dissolved in ethanol (8 mL). 10 N NaOH (900 μL, 9.0 mmol) is added and the contents heated to 60° C. for 2 hrs. The reaction is cooled to r.t. and the pH adjusted to ˜4 with 2 N HCl. The contents are partioned between aq. NH4Cl (10%, 100 mL) and ethyl acetate (100 mL). The aqueous layer is further extracted with ethyl acetate (2×75 mL). The organic fractions are combined and washed with sat. aq. NH4Cl (2×125 mL), dried over MgSO4, filtered and reduced under vacuum to an oil. The crude material is purified by flash chromatography (silica, 6% methanol in dichloromethane) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.29-8.21 (m, 2H), 7.82 (d, 1H), 7.75 (t, 1H), 7.56 (dd, 1H), 7.50 (d, 1H), 7.15 (dd, 2H), 7.00 (dd, 1H), 4.79 (s, 2H), 4.61 (s, 2H), 4.55 (s, 2H), 3.70-3.47 (m, 4H), 2.31 (s, 3H), 1.95 (m, 2H). MS (ESI) 396 (M+H)+.

1. temperatureThe reaction is cooled to r.t.
2. extractionThe aqueous layer is further extracted with ethyl acetate (2×75 mL)
3. washwashed with sat. aq. NH4Cl (2×125 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customThe crude material is purified by flash chromatography (silica, 6% methanol in dichloromethane)