Sodium hydride → 2-Chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine

HRID 2278916Notes

Reaction equation

HRID 2278916 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][N:5]=1.[Cl:11][C:12]1[C:13](F)=[CH:14][C:15]([F:21])=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1>CN(C=O)C.CCOC(C)=O>[Cl:3][C:4]1[CH:9]=[C:8]([O:10][C:13]2[CH:14]=[C:15]([F:21])[C:16]([N+:18]([O-:20])=[O:19])=[CH:17][C:12]=2[Cl:11])[CH:7]=[CH:6][N:5]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 738671-Chloro-2,4-difluoro-5-nitrobenzeneHCID 178516507HCID 178516507, compound

Product 1

HCID 866416872-Chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridineYield 45.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. suspension of NaH (60% in mineral oil, 0.620 g, 15.5 mmol) in DMF (30 mL) was treated portion-wise with of 2-chloro-4-hydroxypyridine (1.339 g, 10.33 mmol), stirred at 0° C. for 0.5 h, slowly warmed to RT, treated with a solution of 5-chloro-2,4-difluoronitrobenzene (2 g, 10.33 mmol) in DMF (4.4 mL) and heated at 90° C. for 15 h. The mixture was cooled to RT, diluted with EtOAc, washed with 10% LiCl (3×), then brine (2×), dried over MgSO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford 2-chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine (1.415 g, 45%). 1H NMR (400 MHz, DMSO-d6): δ 8.56 (dd, 1 H), 8.35 (dd, 1 H), 7.88 (dd, 1 H), 7.32 (dd, 1 H), 7.18 (m, 1H); MS (ESI) m/z: 303.0 (M+H+).

Workup

  1. temperatureslowly warmed to RT
  2. temperatureheated at 90° C. for 15 h
  3. temperatureThe mixture was cooled to RT
  4. washwashed with 10% LiCl (3×)
  5. dry with materialbrine (2×), dried over MgSO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-55b6c362e47846b698e119c507d2be7f
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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