Potassium Carbonate → Methyl 3-(4-fluoro-2-nitrophenylamino)-2-methylpropanoate

HRID 1485434Notes

Reaction equation

HRID 1485434 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[NH2:12][CH2:13][CH:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([NH:12][CH2:13][CH:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 677672,5-DifluoronitrobenzeneHCID 10486829Methyl 3-amino-2-methylpropanoate

Product 1

HCID 70978244Methyl 3-(4-fluoro-2-nitrophenylamino)-2-methylpropanoateYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,4-difluoro-2-nitrobenzene (14.3 g, 90 mmol) in tetrahydrofuran (250 mL) was added methyl 3-amino-2-methylpropanoate (10.5 g, 90 mmol) and potassium carbonate (24.8 g, 180 mmol). The reaction mixture was heated to reflux and stirred for 15 hours. Then the mixture was concentrated in vacuo, and the residue was dissolved in water (250 mL), extracted with ethyl acetate (100 mL*3). The combined organic layers was separated, dried over anhydrous sodium sulfate, and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1) to afford methyl 3-(4-fluoro-2-nitrophenylamino)-2-methylpropanoate as a red solid (14.0 g, 61%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. concentrationThen the mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in water (250 mL)
  5. extractionextracted with ethyl acetate (100 mL*3)
  6. customThe combined organic layers was separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customto give a residue
  10. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1)

Sources & evidence

ORD record
ord-06973f7ca4a84b699385c34c4f93b257
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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