Phosphorus oxybromide → HCID 86617065, compound

HRID 2077134Notes

Reaction equation

HRID 2077134 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](O)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].P(Br)(Br)([Br:30])=O>C(#N)C>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([Br:30])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 24613Phosphorus oxybromideHCID 178450852HCID 178450852, compound

Product 1

HCID 86617065HCID 86617065, compoundYield 10.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-(4-fluoro-phenoxy)-1,4-dihydroxy-isoquinoline-3-carboxylic acid butyl ester (7.43 g, 20 mmol, prepared according to US 2004/0254215 A1 or scheme), POBr3 (17.38 g, 60 mmol), and anhydrous acetonitrile (140 mL) was refluxed with stirring for 60 minutes before it was concentrated in vacuo. To the residue was added ethyl acetate (400 mL), NaHCO3 (60 g), and then water in small portions (400 mL) with stirring. After stirring for 30 min at room temperature the mixture was filtered through a pad of celite. The organic phase of the filtrate was separated, and dried over MgSO4. Then silica gel was added and the mixture was concentrated in vacuo. The residue was added on top of a short column filled with silica gel. Elution using CH2Cl2 as the solvent gave the title compound as an off-white solid (930 mg); 1H NMR (CDCl3, 200 MHz): δ=11.76 (s, 1H), 8.22 (d, J=9.4 Hz, 1H), 7.61 (d, J=2.3 Hz, 1H), 7.50 (dd, J=9.0, 2.3 Hz, 1H), 7.10 to 7.13 (m, 4H), 4.46 (t, J=7.0 Hz, 2H), 1.85 (m, 2H), 1.45 (m, 2H), 0.99 (t, J=7.4 Hz, 3H).

Workup

  1. temperaturewas refluxed
  2. concentrationwas concentrated in vacuo
  3. additionTo the residue was added ethyl acetate (400 mL), NaHCO3 (60 g)
  4. stirringwater in small portions (400 mL) with stirring
  5. stirringAfter stirring for 30 min at room temperature the mixture
  6. filtrationwas filtered through a pad of celite
  7. customThe organic phase of the filtrate was separated
  8. dry with materialdried over MgSO4
  9. additionThen silica gel was added
  10. concentrationthe mixture was concentrated in vacuo
  11. additionThe residue was added on top of a short column
  12. additionfilled with silica gel
  13. washElution

Sources & evidence

ORD record
ord-5640dd416dd34f688ad96e311cd79f3e
Source dataset
uspto-grants-2011_04
Patent number
US07928120B2

Reaction notes

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