Sodium hydride → HCID 59287320, compound

HRID 1020851Notes

Reaction equation

HRID 1020851 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.[H-].[Na+].[N+]([C:15]1[CH:16]=[C:17]([CH3:22])[N+:18]([O-:21])=[CH:19][CH:20]=1)([O-])=O>CN1CCCC1=O.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:15]2[CH:20]=[CH:19][N+:18]([O-:21])=[C:17]([CH3:22])[CH:16]=2)=[C:4]([F:9])[CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 95291Pyridine, 2-methyl-4-nitro-, 1-oxideHCID 27249814-Bromo-2-fluorophenol

Product 1

HCID 59287320HCID 59287320, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of 4-bromo-2-fluorophenol (3.44 ml, 31.41 mmol) in N-methylpyrrolidone (20 ml) at r.t., was added sodium hydride (1.34 g, 56 mmol, 60% in mineral oil) portionwise. After stirring for 20 min, 4-nitro-2-picoline N-oxide (5.6 g, 36.12 mmol) was added. The reaction mixture was heated at 180° C. for 60 min. under microwave irradiation. After cooling to r.t. the mixture was diluted with EtOAc (250 ml), washed with water (250 ml) and then extracted with additional EtOAc (2×150 ml). The combined organic extracts were dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D25 (4.36 g, 47%).

Workup

  1. temperatureAfter cooling to r.t. the mixture
  2. washwashed with water (250 ml)
  3. extractionextracted with additional EtOAc (2×150 ml)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. customthe solvent evaporated in vacuo
  6. customThe crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent)
  7. customThe desired fractions were collected
  8. concentrationconcentrated in vacuo
  9. customto yield intermediate compound D25 (4.36 g, 47%)

Sources & evidence

ORD record
ord-903a266b8c854f33a4542a931289efa2
Source dataset
uspto-grants-2014_05
Patent number
US08716480B2

Reaction notes

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