4-Chloro-2-nitroaniline → HCID 59349482, compound

HRID 415053Notes

Reaction equation

HRID 415053 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[H-].[Na+].Cl[C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[C:14]([N+:19]([O-:21])=[O:20])[CH:13]=1>CC(N(C)C)=O>[N+:19]([C:14]1[CH:13]=[C:12]([O:1][CH2:2][C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)[CH:18]=[CH:17][C:15]=1[NH2:16])([O-:21])=[O:20]

Participants

5

Reactant 3

HCID 69794-Chloro-2-nitroanilineHCID 114724-HydroxymethylpyridineHCID 24758Sodium hydride

Product 1

HCID 59349482HCID 59349482, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

4-Hydroxymethylpyridine (50 mmoles, 5.45 g, 1 equivalent, commercially available from Aldrich) was added in a drop wise fashion to a stirred suspension of 60% sodium hydride (in oil) (55 mmoles, 2.2 g, 1.1 equivalent) in anhydrous DMA (100 ml) at room temperature, over a period of 5 minutes. Upon completion of addition the resulting green reaction mixture was stirred at room temperature for 20 minutes. 4-chloro-2-nitroaniline (50 mmoles, 8.62 g, 1 equivalent) was added to the stirred green reaction mixture over the course of 10 minutes. The reaction mixture was stirred at 80° C. for 12 hours. The reaction mixture was allowed to cool to room temperature, poured into ice-water (300 ml) and extracted with ethyl acetate (3×200 ml). The combined ethyl acetate solutions were washed with water (2×100 ml) and saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The resulting crude material was purified by silica flash column chromatography using 20% ethyl acetate-hexane to give 1.576 g of 2-nitro-4-(pyridin-4-ylmethoxy)aniline. (Yield 13%). 1H-NMR (400 MHz, DMSO-d6) 8.60 (d, 2H), 7.91 (d, 1H), 7.52 (br s, 2H), 7.43 (d, 2H), 6.50 (d, 1H), 6.34 (d, 1H), 5.31 (s, 2H). (MS (EI): 246 (MH+).

Workup

  1. additionUpon completion of addition the resulting green reaction mixture
  2. stirringThe reaction mixture was stirred at 80° C. for 12 hours
  3. temperatureto cool to room temperature
  4. extractionextracted with ethyl acetate (3×200 ml)
  5. washThe combined ethyl acetate solutions were washed with water (2×100 ml) and saturated sodium chloride solution (100 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe resulting crude material was purified by silica flash column chromatography

Sources & evidence

ORD record
ord-53c6baf515f0411f86887a54f305ef5b
Source dataset
uspto-grants-2012_01
Patent number
US08088767B2

Reaction notes

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