3-Nitroanisole → 6-Nitro-o-anisidine

HRID 7088

Reaction equation

HRID 7088 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([O:10][CH3:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl.CO[NH2:15].CC(C)([O-])C.[K+]>CN(C=O)C.[Cu]Cl>[NH2:15][C:5]1[C:6]([O:10][CH3:11])=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2]

Participants

6

Reactant 3

HCID 111403-NitroanisoleHCID 521874O-Methylhydroxylamine hydrochlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 854916-Nitro-o-anisidineYield 50.5%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A suspension of 3-nitroanisole (1.550 g, 10.12 mmol) and O-methylhydroxylamine hydrochloride (1.078 g, 12.91 mmol) in DMF (15 mL) was added to a cold (0° C.) solution of potassium tert-butoxide (5.870 g, 52.30 mmol) and copper(I) chloride (0.200 g, 2.02 mmol) in DMF (35 mL). The cooling bath was removed and the resultant slurry was stirred at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous NH4Cl (50 mL) and the mixture was extracted with CH2Cl2 (4×50 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (5:1 hexanes-ethyl acetate) followed by radial chromatography on silica gel (2 mm plate, 5:1 hexanes-ethyl acetate) provided 0.860 g (50%) of 2-amino-3-methoxy-nitrobenzene as a red solid. 1H NMR (CDCl3) □ 3.92 (s, 3H), 6.44 (br s, 2H), 6.61 (dd, 1H, J=9.0, 9.0 Hz), 6.88 (d, 1H, J=9.0 Hz), 7.74 (d, 1H, J=9.0 Hz).

Workup

  1. customThe cooling bath was removed
  2. additionThe reaction mixture was poured into saturated aqueous NH4Cl (50 mL)
  3. extractionthe mixture was extracted with CH2Cl2 (4×50 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification of the crude material by column chromatography on silica gel (5:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-23441250a17843d69020cc61a28af1cf
Source dataset
uspto-grants-2006_08
Patent number
US07084155B2

Linked notes

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