3-Bromo-4-chloropyridine → 3-Bromo-4-(2,5-difluoro-4-nitrophenoxy)pyridine

HRID 1046000Notes

Reaction equation

HRID 1046000 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([F:11])=[CH:4][C:3]=1[OH:12].[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1Cl>ClC1C=CC=CC=1>[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[O:12][C:3]1[CH:4]=[C:5]([F:11])[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[F:1]

Participants

4

Reactant 2

HCID 8176963-Bromo-4-chloropyridineHCID 27824902,5-Difluoro-4-nitrophenol

Product 1

HCID 673986343-Bromo-4-(2,5-difluoro-4-nitrophenoxy)pyridineYield 38%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
145 °C

Procedure

2,5-Difluoro-4-nitro-phenol (1.739 g, 9.93 mmol) and 3-bromo-4-chloro-pyridine (0.637 g, 3.31 mmol) were dissolved in chlorobenzene (6 mL) and heated at 145° C. overnight. The solvent was removed under reduced pressure and the residue partitioned between EtOAc and 10% aqueous K2CO3. The mixture was extracted with EtOAc (2×), and the combined organic extracts were washed with 10% aqueous K2CO3 and brine, dried, evaporated and purified by silica gel chromatography (hexanes/EtOAc) to yield 3-bromo-4-(2,5-difluoro-4-nitrophenoxy)pyridine (414 mg, 38% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.84 (s, 1H), 8.51-8.45 (m, 2H), 7.82-7.78 (m, 1H), 7.22 (d, 1H); MS (ESI) m/z: 331.0 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue partitioned between EtOAc and 10% aqueous K2CO3
  3. extractionThe mixture was extracted with EtOAc (2×)
  4. washthe combined organic extracts were washed with 10% aqueous K2CO3 and brine
  5. customdried
  6. customevaporated
  7. custompurified by silica gel chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-8730b0bb0b28439196ddc85860035fa1
Source dataset
uspto-grants-2013_10
Patent number
US08569319B2

Reaction notes

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