Hydrochloric Acid → Ethyl 8-methoxy-3-nitronaphthalene-2-carboxylate

HRID 1968762Notes

Reaction equation

HRID 1968762 reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH2:5][CH2:6][N+:7]([O-:9])=[O:8])[CH3:2].[Na].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]=O)[C:15]=1[CH:22]=O.Cl>CCO>[CH2:1]([O:3][C:4]([C:5]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:20][C:16]2[C:15](=[C:14]([O:13][CH3:12])[CH:19]=[CH:18][CH:17]=2)[CH:22]=1)=[O:10])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5360545SodiumHCID 11804910Ethyl 3-nitropropionateHCID 203918283-Methoxyphthalaldehyde

Product 1

HCID 66882859Ethyl 8-methoxy-3-nitronaphthalene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

A solution of 3-nitro-propionic acid ethyl ester (16.25 g, 110.45 mmol, 4.0 equiv) in EtOH (150 ml) was added at 0° C. under an atmosphere of argon to a freshly prepared solution of sodium (2.54 g, 110.45 mmol, 4.0 equiv) in EtOH (110 ml). After 15 minutes, a solution of 3-methoxy-benzene-1,2-dicarbaldehyde (4.53 g, 27.61 mmol) in EtOH (150 ml) was added at 0° C. The reaction mixture was warmed to room temperature, and after 40 minutes, TLC analysis indicated complete conversion. 2 N aqueous HCl (55 ml, 4 equiv) was carefully added at 0° C., and the mixture was extracted with EtOAc (1.5 liter in total). The combined organic layers were washed with concentrated aqueous NH4Cl solution (200 ml), brine (400 ml), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash chromatography (gradient of toluene/hexane 5:5 to 10:0) to afford the title compound (0.942 g, 12%, inseparable 1:1.15 mixture of regioisomers A:B) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ=8.87 (s, 1H isomer A), 8.69 (s, 1H isomer B), 8.33 (s, 1H isomer B), 8.15 (s, 1H isomer A), 7.64-7.59 (m, 1H isomer A+1 H isomer B), 7.53 (d, J=8.1 Hz, 1H isomer B), 7.51 (d, J=8.3 Hz, 1H isomer A), 7.02 (d, J=6.5 Hz, 1H isomer B), 7.00 (d, J=7.8 Hz, 1H isomer A), 4.42 (q, J=7.3 Hz, 2H isomer A), 4.41 (q, J=7.1 Hz, 2H isomer B), 4.04 (s, 3H isomer A), 4.03 (s, 3H isomer B), 1.38 (t, J=6.3 Hz, 3H isomer A+3H isomer B). MS (ES+): 276 (M+H)+.

Workup

  1. waitafter 40 minutes
  2. extractionthe mixture was extracted with EtOAc (1.5 liter in total)
  3. washThe combined organic layers were washed with concentrated aqueous NH4Cl solution (200 ml), brine (400 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash chromatography (gradient of toluene/hexane 5:5 to 10:0)

Sources & evidence

ORD record
ord-c94c4516862e4cfe8b5e5a774bb7c21b
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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