Methanol → Methyl 5-fluoro-2-hydroxy-3-nitrobenzoate

HRID 415168Notes

Reaction equation

HRID 415168 reaction equation
S(Cl)(Cl)=O.[F:5][C:6]1[CH:7]=[C:8]([N+:16]([O-:18])=[O:17])[C:9]([OH:15])=[C:10]([CH:14]=1)[C:11]([OH:13])=[O:12].[CH3:19]O>>[F:5][C:6]1[CH:7]=[C:8]([N+:16]([O-:18])=[O:17])[C:9]([OH:15])=[C:10]([CH:14]=1)[C:11]([O:13][CH3:19])=[O:12]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 152546965-Fluoro-2-hydroxy-3-nitrobenzoic acid

Product 1

HCID 57336604Methyl 5-fluoro-2-hydroxy-3-nitrobenzoateYield 80%

Procedure

Thionyl chloride (5.88 g, 49.4 mmol) was added dropwise to anhydrous methanol (45 mL) at 5° C. The mixture was stirred at this temperature for 30 min. Then 5-fluoro-2-hydroxy-3-nitrobenzoic acid was added to the mixture and the resulting mixture was heated to reflux for 24 hr. Solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (100 mL), washed with water (100 mL×3), brine (50 mL), dried over anhydrous sodium sulfate and concentrated to give crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=100:1 to 5:1) to give methyl 5-fluoro-2-hydroxy-3-nitrobenzoate (3.4 g, yield 80% for two steps). 1H-NMR (400 MHz, CDCl3-d) δ 4.04 (s, 3H), 7.88-7.90 (dd, J1=7.6 Hz, J2=3.2 Hz, 1H), 7.93-7.96 (dd, J1=7.6 Hz, J2=3.2 Hz, 1H), 11.74 (s, 1H); LC-MS (ESI) m/z 216 [M+1]+.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 24 hr
  3. customSolvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with water (100 mL×3), brine (50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto give crude product
  9. customThe crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=100:1 to 5:1)

Sources & evidence

ORD record
ord-9f8852ad20a4475c9a3d496f967e62d1
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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