Sulfuric Acid → 1-Fluoro-4-(1-methoxyethyl)-2-nitrobenzene

HRID 58197Notes

Reaction equation

HRID 58197 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:10])[CH3:9])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].S(=O)(=O)(O)O.[CH3:19]COC(C)=O.O>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:10][CH3:19])[CH3:9])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 179959151-(4-Fluoro-3-nitrophenyl)ethanolHCID 22728543Water ethylacetate

Product 1

HCID 179959131-Fluoro-4-(1-methoxyethyl)-2-nitrobenzeneYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

1-(4-fluoro-3-nitrophenyl)ethanol (870 g, 4.7 mmol) was dissolved in MeOH (10 ml) and concentrated sulfuric acid (2.5 ml, 47 mmol) was added carefully. The reaction mixture was heated at 150° C. using microwave (Biotage Initiator) for 5 minutes. After cooling to room temperature, the reaction mixture was poured into EtOAc/water. The organic layer was washed with brine, dried over MgSO4 and evaporated. The resulting material was purified by flash chromatography on silica eluting with 0% to 50% EtOAc/Hexane to afford the title compound (664 mg, yield: 71%). 1H-NMR (400 MHz, CDCl3) δ 1.45 (d, 3H) 3.27 (s, 3H) 4.36 (q, 1H) 7.28-7.32 (m, 1H) 7.56-7.63 (m, 1H) 7.98-8.04 (m, 1H)

Workup

  1. customfor 5 minutes
  2. temperatureAfter cooling to room temperature
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe resulting material was purified by flash chromatography on silica eluting with 0% to 50% EtOAc/Hexane

Sources & evidence

ORD record
ord-1527a245572a4841aaa0af8fc180256a
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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