p-Fluoronitrobenzene → HCID 58528840, compound

HRID 1430991Notes

Reaction equation

HRID 1430991 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([O:10][CH:11]([CH3:13])[CH3:12])[CH:7]=[C:6]([OH:14])[CH:5]=1.C([O-])([O-])=O.[K+].[K+].F[C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1>CC(C)=O>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:5]=[C:6]([O:14][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)[CH:7]=[C:8]([O:10][CH:11]([CH3:12])[CH3:13])[CH:9]=1

Participants

5

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 11430Potassium CarbonateHCID 23072925Methyl 3-hydroxy-5-isopropoxybenzoate

Product 1

HCID 58528840HCID 58528840, compoundYield 99.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 3-hydroxy-5-isopropoxy-benzoic acid methyl ester (7.00 g, 33.3 mmol) in acetone (80 mL) was added K2CO3 (5.06 g, 36.6 mmol) and 1-fluoro-4-nitrobenzene (3.53 mL, 33.3 mmol) at rt. The resulting mixture was refluxed for 12 hr. Then the mixture was filtered through a pad of Celite to remove insoluble salts and the cake was rinsed with acetone. Combined filtrates were concentrated under vacuum to afford a residue which was purified by silica gel flash chromatography (7.5×30 cm, hexane/EtOAc, v/v 10:1, 5:1). Fractions containing the mono-alkylation product were pooled and concentrated to give 3-isopropoxy-5-(4-nitro-phenoxy)-benzoic acid methyl ester (11.0 g, 44%) as a brown oil. 1H NMR (300 MHz, CDCl3): δ 8.22 (d, J=9 Hz, 2H), 7.43 (dd, J=1, 2 Hz, 1H), 7.29 (dd, J=1, 2 Hz, 1H), 7.04 (d, J=9 Hz, 2H), 6.80 (dd, J=2, 2 Hz, 1H), 4.56-4.64 (m, 1H). 3.90 (s, 3H), 1.35 (d, J=6 Hz, 6H).

Workup

  1. temperatureThe resulting mixture was refluxed for 12 hr
  2. filtrationThen the mixture was filtered through a pad of Celite
  3. customto remove insoluble salts
  4. washthe cake was rinsed with acetone
  5. concentrationCombined filtrates were concentrated under vacuum
  6. customto afford a residue which
  7. customwas purified by silica gel flash chromatography (7.5×30 cm, hexane/EtOAc, v/v 10:1, 5:1)
  8. additionFractions containing the mono-alkylation product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-220749bca8b040e09c2518d153d8695e
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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