Boron Trichloride → 648896-69-9

HRID 872233Notes

Reaction equation

HRID 872233 reaction equation
B(Cl)(Cl)Cl.[Cl:5][C:6]1[CH:15]=[C:14]([Cl:16])[C:13]([O:17]C(C)C)=[C:12]2[C:7]=1[CH:8]=[CH:9][C:10]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[N:11]2>ClCCl>[Cl:5][C:6]1[CH:15]=[C:14]([Cl:16])[C:13]([OH:17])=[C:12]2[C:7]=1[CH:8]=[CH:9][C:10]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[N:11]2

Participants

4

Reactant 2

HCID 25135Boron Trichloride2×HCID 579393755,7-Dichloro-8-[(propan-2-yl)oxy]-2-(pyridin-2-yl)quinoline

Product 1

HCID 135524494648896-69-9

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

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, 1 H), 9.21 (d, J=9, 1 H), 8.30-8.62 (m, 3 H), 8.12 (m, 1 H), 7.88 (s, 1 H), 7.62 (m, 1 H).

Workup

  1. temperatureto warm to RT
  2. waitAfter 24 h
  3. stirringstirring
  4. waitresumed for a further 4 h
  5. customThe reaction was quenched with methanol (10 mL)
  6. customthe volatiles removed in vacuo
  7. additionThe hydrochloride salt (1.68 g) and water (20 mL) was then treated with saturated sodium bicarbonate until the pH of the solution
  8. extractionextracted with ethyl acetate (30 mL×3)
  9. customdried
  10. customThe residue obtained
  11. customafter solvent removal
  12. washwas washed with methanol

Sources & evidence

ORD record
ord-e1beeba3cf6d48fa83ba01bac6246d46
Source dataset
uspto-grants-2015_03
Patent number
US08975278B2

Reaction notes

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