Reaction #84064

Reaction equation

3-chloro-4-(6-methoxyquinolin-2-yl)benzoic acid

AlCl3

→

3-chloro-4-(6-hydroxyquinolin-2-yl)benzoic acid

Yield 18.0%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was refluxed overnight
2. 2
   OtherThe mixture was quenched with saturated NH4Cl (10 mL)
3. 3
   Extractionthe aqueous layer was extracted with CH2Cl2/MeOH (v/v=10:1, 30 mL×3)
4. 4
   WashThe combined organic layer was washed with brine
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   Otherto give the crude product, which
9. 9
   Otherwas purified by prep-HPLC (0.1% TFA as additive)

Procedure

To a suspension of 3-chloro-4-(6-methoxyquinolin-2-yl)benzoic acid (150 mg, 0.479 mmol) in anhydrous CH2Cl2 (5 mL) was added AlCl3 (320 mg, 2.40 mmol). The reaction mixture was refluxed overnight. The mixture was quenched with saturated NH4Cl (10 mL) and the aqueous layer was extracted with CH2Cl2/MeOH (v/v=10:1, 30 mL×3). The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated to give the crude product, which was purified by prep-HPLC (0.1% TFA as additive) to give 3-chloro-4-(6-hydroxyquinolin-2-yl)benzoic acid (25 mg, yield 18%). 1H NMR (DMSO, 400 MHz): δ 10.20 (brs, 1H), 8.30 (d, J=8.4 Hz, 1H), 8.10-8.00 (m, 2H), 7.95 (d, J=9.2 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.38 (dd, J=6.4, 2.8 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), MS (ESI): m/z 299.9 [M+H]+.

Source