Ethyl bromoacetate → ethyl 2-(4-formyl-2-nitrophenoxy)acetate

HRID 1271204Notes

Reaction equation

HRID 1271204 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[H-].[Na+].Br[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>O1CCCC1.CN(C=O)C>[CH2:20]([O:19][C:17](=[O:18])[CH2:16][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11])[CH3:21]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 181694-Hydroxy-3-nitrobenzaldehydeHCID 24758Sodium hydride

Product 1

HCID 5305379ethyl 2-(4-formyl-2-nitrophenoxy)acetate

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a solution of 4-hydroxy-3-nitrobenzaldehyde (5.00 g, 29.9 mmol) in tetrahydrofuran/DMF (300 mL/120 mL) was added NaH (60%, 1.32 g, 32.9 mmol), followed by ethyl bromoacetate (5.49 g, 3.65 mL, 32.9 mmol). The mixture was heated at reflux for 20 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (200 mL), acidified to pH 2 with 1N HCl, and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×50 mL), the organic extracts were combined and washed with saturated NaHCO3 (2×50 mL), brine (1×50 mL), dried over MgSO4, and concentrated to an amber oil. Purification of the residue by silica gel flash chromatography (25% ethyl acetate/hexanes) afforded the title compound. 1H NMR (DMSO-d6) δ 1.91 (t, J=7.08 Hz, 3H), 4.16 (q, J=7.08 Hz, 2H), 5.15 (s, 2H), 7.50 (d, J=8.79 Hz, 1H), 8.12–8.14 (m, 1H), 8.42 (d, J=1.95 Hz, 1H), 9.93 (s, 1H) ppm. MS: M+−1=252.1 Da.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 20 hours
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  7. washwashed with saturated NaHCO3 (2×50 mL), brine (1×50 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated to an amber oil
  10. customPurification of the residue by silica gel flash chromatography (25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4800c6b161f945d3bb1cdc43387f0736
Source dataset
uspto-grants-2007_04
Patent number
US07205295B2

Reaction notes

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