Reaction #710592

Reaction equation

boron trichloride

Boron trichloride

5,7-dichloro-8-isopropoxy-2-(2-pyridyl)quinoline

→

5,7-dichloro-8-hydroxy-2-(2-pyridyl)quinoline

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Temperatureto warm to RT
2. 2
   workup.WAITAfter 24 h
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITresumed for a further 4 h
5. 5
   OtherThe reaction was quenched with methanol (10 mL)
6. 6
   Otherthe volatiles removed in vacuo
7. 7
   workup.ADDITIONThe hydrochloride salt (1.68 g) and water (20 mL) was then treated with saturated sodium bicarbonate until the pH of the solution
8. 8
   Extractionextracted with ethyl acetate (30 mL×3)
9. 9
   Otherdried
10. 10
    OtherThe residue obtained
11. 11
    Otherafter solvent removal
12. 12
    Washwas washed with methanol

Procedure

Boron trichloride (27 mL of a 1 M solution in dichloromethane, 27.6 mmol) was added dropwise to a solution of 5,7-dichloro-8-isopropoxy-2-(2-pyridyl)quinoline 15 (1.83 g, 5.51 mmol) in dichloromethane (30 mL) at 0° C. under an atmosphere of nitrogen. The mixture was stirred at 0° C. for 1 h and then allowed to warm to RT. After 24 h, some starting material was still present (by TLC analysis). More boron trichloride (14 mL) was added and stirring resumed for a further 4 h. The reaction was quenched with methanol (10 mL) and the volatiles removed in vacuo. The process was repeated until the residue reached constant weight. This gave 5,7-dichloro-8-hydroxy-2-(2-pyridyl)quinoline as the hydrochloride salt. The hydrochloride salt (1.68 g) and water (20 mL) was then treated with saturated sodium bicarbonate until the pH of the solution was 8. The mixture was the extracted with ethyl acetate (30 mL×3) and dried. The residue obtained after solvent removal was washed with methanol. This provided 5,7-dichloro-8-hydroxy-2-(2-pyridyl)quinoline (PBT 1052) as an off-white solid (1.25 g, 78%), m.p.>230° C. 1H NMR (DMSO-d6, 200 MHz): δ 10.8 (br, 1H), 9.21 (d, J=9, 1H), 8.30-8.62 (m, 3H), 8.12 (m, 1H), 7.88 (s, 1H), 7.62 (m, 1H).

Source