Sodium Hydroxide → 4-Chloro-6-(trifluoromethoxy)quinoline

Temperature

130 °C

In a 25 mL round bottom flask was dissolved 6-(trifluoromethoxy)quinolin-4(1H)-one (0.50 g, 2.18 mmol) in POCl3 (3.05 mL). A reflux condenser was attached and the reaction mixture was stirred at 130° C. for 3 hours. The reaction turned dark brown and became homogeneous. The reaction was cooled to RT, poured slowly into ice bath while stirring. A thick gum resulted, which was basified with 6N NaOH to give a dark brown solution. The solution was extracted into ethyl acetate, washed 1× water, 1×NaCl, dried with Na2SO4, filtered through flitted funnel, concentrated down. The crude material was purified using an Isco silica gel chromatography system eluting with a solvent gradient of 0-100% CH2Cl2:MeOH(90:10)/CH2Cl2. The product fractions were concentrated down to yield 4-chloro-6-(trifluoromethoxy)quinoline as an orange oil. MS [M+H]=248.0; Calc'd 247.6 for C10H5ClF3NO.

1. customA reflux condenser was attached
2. temperatureThe reaction was cooled to RT
3. additionpoured slowly into ice bath
4. stirringwhile stirring
5. customA thick gum resulted
6. customto give a dark brown solution
7. extractionThe solution was extracted into ethyl acetate
8. washwashed 1× water, 1×NaCl
9. dry with materialdried with Na2SO4
10. filtrationfiltered through flitted funnel
11. concentrationconcentrated down
12. customThe crude material was purified
13. washeluting with a solvent gradient of 0-100% CH2Cl2:MeOH(90:10)/CH2Cl2
14. concentrationThe product fractions were concentrated down

ORD record

ord-f3c0aee5af66459b8c6b48097a98851c

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08557816B2