Pyridine, hydrofluoride (1:1) → 5-Bromo-6-ethoxy-8-fluoro-1,7-naphthyridine

HRID 1881763Notes

Reaction equation

HRID 1881763 reaction equation
[Br:1][C:2]1[C:11]([O:12][CH2:13][CH3:14])=[N:10][C:9](N)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.N([O-])=O.[Na+].C([O-])(O)=O.[Na+].[FH:25].N1C=CC=CC=1>>[Br:1][C:2]1[C:11]([O:12][CH2:13][CH3:14])=[N:10][C:9]([F:25])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

5

Reactant 4

HCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 591431045-Bromo-6-ethoxy-1,7-naphthyridin-8-amine

Product 1

HCID 591429785-Bromo-6-ethoxy-8-fluoro-1,7-naphthyridineYield 85%

Conditions

Temperature
0 °C

Procedure

To a 100 mL round bottom flask was added 5-bromo-6-ethoxy-1,7-naphthyridin-8-amine (500 mg, 1.86 mmol), followed by pyridine hydrogen fluoride (10 mL). The mixture was cooled to 0° C. and sodium nitrite (0.154 mg, 2.24 mmol) was added in portions. The mixture was slowly warmed to room temperature over a period of 3 h. The reaction was neutralized with saturated NaHCO3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The resultant residue was purified by silica gel to yield 5-bromo-6-ethoxy-8-fluoro-1,7-naphthyridine as a pale yellow solid (430 mg, 1.59 mmol, 85%). 1H NMR (400 MHz, CDCl3): δ ppm 8.87 (d, J=3.52 Hz, 1H), 8.42 (d, J=8.79 Hz, 1H), 7.65 (dd, J=8.13, 3.30 Hz, 1H), 4.55 (q, J=7.03 Hz, 2H), 1.49 (t, J=7.03 Hz, 3H). LC/MS m/z 273 [M+H].

Workup

  1. temperatureThe mixture was slowly warmed to room temperature over a period of 3 h
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe resultant residue was purified by silica gel

Sources & evidence

ORD record
ord-b2e5213718914bbd8b9fbd7a0f72ea55
Source dataset
uspto-grants-2012_11
Patent number
US08318941B2

Reaction notes

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