Water → N-(2-bromo-6-nitrophenyl)-5-fluoropyridin-3-amine

HRID 2036663Notes

Reaction equation

HRID 2036663 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1F.[NH2:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([F:19])[CH:18]=1.CC(C)([O-])C.[K+].O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[NH:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([F:19])[CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5744505-Fluoro-3-pyridinamineHCID 23665647Potassium tert-butoxideHCID 404274461-Bromo-2-fluoro-3-nitrobenzene

Product 1

HCID 58459289N-(2-bromo-6-nitrophenyl)-5-fluoropyridin-3-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-bromo-2-fluoro-3-nitrobenzene (5.69 g, 25.9 mmol) and 3-amino-5-fluoropyridine (2.6373 g, 23.53 mmol) in DMF (39.2 mL) was added potassium tert-butoxide (5.28 g, 47.1 mmol) and the solution was stirred under nitrogen at rt overnight. After 5 additional h, the mixture was poured into water (150 mL) and extracted with EtOAc (2×100 mL). The organic extract was dried over MgSO4. The solution was filtered and concentrated in vacuo to provide the crude material as a orange solid. The orange solid was purified by chromatography through a Redi-Sep™ pre-packed silica gel column (120 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide N-(2-bromo-6-nitrophenyl)-5-fluoropyridin-3-amine as orange syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (1H, s), 8.09 (1H, dd, J=8.1, 1.5 Hz), 8.03 (1H, dd, J=8.2, 1.4 Hz), 7.97 (1H, d, J=2.5 Hz), 7.88 (1H, t, J=1.9 Hz), 7.44 (1H, t, J=8.1 Hz), 6.77 (1H, dt, J=11.2, 2.3 Hz); LC-MS (ESI) m/z 312.0 [M+H (79Br)]+ and 313.9 [M+H (81Br)]+.

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. extractionThe organic extract
  3. dry with materialwas dried over MgSO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customto provide the crude material as a orange solid
  7. customThe orange solid was purified by chromatography through a Redi-Sep™ pre-packed silica gel column (120 g)
  8. washeluting with a gradient of 0% to 50% EtOAc in hexane

Sources & evidence

ORD record
ord-811727f5a9f24732baaeb8125e3908fb
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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