Nitric Acid → Methyl 4-fluoro-3-methyl-5-nitrobenzoate

HRID 60071Notes

Reaction equation

HRID 60071 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].[N+:13]([O-])([OH:15])=[O:14]>OS(O)(=O)=O>[F:1][C:2]1[C:11]([N+:13]([O-:15])=[O:14])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12]

Participants

4

Reactant 2

HCID 944Nitric AcidHCID 18788764Methyl 4-fluoro-3-methylbenzoate

Product 1

HCID 60150318Methyl 4-fluoro-3-methyl-5-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Conditions

Temperature
0 °C

Procedure

Concentrated H2SO4 (17.5 mL) was slowly added to methyl 4-fluoro-3-methylbenzoate (12.8 g, 76 mmol) and the mixture was cooled to 0° C. A solution of fuming HNO3 (69.5%, 11.6 mL) in concentrated H2SO4 (17.5 mL) was then added drop-wise over 10 min. The mixture was stirred for 80 min while slowly warming up to room temperature (reaction completion monitored by TLC). The mixture was slowly poured into ice, the aqueous layer was extracted with CH2Cl2 (3×200 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was purified by column chromatography to afford methyl 4-fluoro-3-methyl-5-nitrobenzoate (I-35a) as a white solid. MS calculated for C9H9FNO4 (M+H+) 214.04. found 214.0.

Workup

  1. temperaturewhile slowly warming up to room temperature
  2. custom(reaction completion monitored by TLC)
  3. additionThe mixture was slowly poured into ice
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×200 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-664dabe9c94046f9a1347b499d63c377
Source dataset
uspto-grants-2016_09
Patent number
US09440957B2

Reaction notes

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