Boron tribromide → 2-Chloro-6-hydroxyquinoline-3-carbaldehyde

HRID 2403687Notes

Reaction equation

HRID 2403687 reaction equation
[Cl:1][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:14]C)[CH:8]=2)[N:3]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:1][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:14])[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 6890792-Chloro-6-methoxyquinoline-3-carbaldehyde

Product 1

HCID 210510652-Chloro-6-hydroxyquinoline-3-carbaldehydeYield 61.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a −78° C. mixture of 2-chloro-6-methoxyquinoline-3-carbaldehyde (4.64 g, 20.9 mmol) in dichloromethane (130 mL) was added boron tribromide (4.0 mL, 42 mmol). The mixture was allowed to warm to room temperature and stir for 4 hours. The reaction was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was then extracted with 2-methyl tetrahydrofuran (3×). The combined organics were filtered, and the filtrate was washed with saturated aqueous sodium bicarbonate (3×) and once with brine. The organics were dried over sodium sulfate, filtered, and concentrated to a yellow solid. The solid was partially dissolved in 2-methyl tetrahydrofuran and filtered. The filtrate was concentrated to a solid and again partially dissolved in 2-methyl tetrahydrofuran, filtered, and concentrated. Purification by flash column chromatography (10-100% ethyl acetate/heptanes) gave the title compound (2.65 g, 61%) as a pale yellow solid. +ESI (M+H) 208.1; 1H NMR (400 MHz, CDCl3, δ): 10.54 (s, 1 H), 8.59 (s, 1 H), 7.98 (d, J=9.17 Hz, 1 H), 7.47 (dd, J=9.17, 2.73 Hz, 1 H), 7.25 (d, J=2.93 Hz, 1 H), 5.57 (br. s., 1 H).

Workup

  1. extractionThe mixture was then extracted with 2-methyl tetrahydrofuran (3×)
  2. filtrationThe combined organics were filtered
  3. washthe filtrate was washed with saturated aqueous sodium bicarbonate (3×) and once with brine
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a yellow solid
  7. dissolutionThe solid was partially dissolved in 2-methyl tetrahydrofuran
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated to a solid
  10. dissolutionagain partially dissolved in 2-methyl tetrahydrofuran
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash column chromatography (10-100% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-b39656a02e5b46f49aca6f2e7d65fdf4
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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