Acetyl chloride → Methyl 4-fluoro-3-nitrobenzoate

HRID 1832064Notes

Reaction equation

HRID 1832064 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[C:14](Cl)(=O)C>CO>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:14])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 679874-Fluoro-3-nitrobenzoic acid

Product 1

HCID 5219721Methyl 4-fluoro-3-nitrobenzoateYield 75.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 1 L 3-necked round bottomed flask equipped with a nitrogen inlet, stirbar, addition funnel and thermocouple was charged with 4-fluoro-3-nitrobenzoic acid (50 g, 0.27 mol) and methanol (300 mL). The system was cooled to 0 C and acetyl choride (27 mL, 0.37 mol) was added dropwise. The system was warmed to room temperature, the addition funnel was replaced with a reflux condensor, and was heated to reflux for 1.5 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaHCO3, and extracted with ethyl acetate. The organic extract was washed with brine, dried with Na2SO4 and concentrated in vacuo to give methyl 4-fluoro-3-nitrobenzoate as an orange solid (40.6 g, 75%). 1H NMR (400 MHz, CD3OD) δ 8.67 ((dd, J=2.2 and 6.8 Hz, 1H), 8.34 (dddd, J=2.2, 4.4, 6.4 and 8.8 Hz, 1H), 7.55 (dd, J=8.8 and 10.8 Hz, 1H), 3.94 (s, 3H) ppm. ES-HRMS m/z 200.02446 (M+H calcd for C8H7FNO4 requires 200.0354). Step 2 Preparation of methyl 3-amino-4-fluorobenzoate

Workup

  1. customA 1 L 3-necked round bottomed flask equipped with a nitrogen inlet
  2. additionstirbar, addition funnel
  3. additionwas added dropwise
  4. temperaturewas heated
  5. temperatureto reflux for 1.5 h
  6. temperatureThe reaction mixture was cooled to room temperature
  7. customquenched with saturated aqueous NaHCO3
  8. extractionextracted with ethyl acetate
  9. extractionThe organic extract
  10. washwas washed with brine
  11. dry with materialdried with Na2SO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-735eeed9276e438d9bf593bb6635594c
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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