Methanol → Methyl 5-amino-2-fluorobenzoate

HRID 239461Notes

Reaction equation

HRID 239461 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(Cl)(Cl)=O.[CH3:16]O>>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:16])=[O:8]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 27359105-Amino-2-fluorobenzoic acid

Product 1

HCID 15621043Methyl 5-amino-2-fluorobenzoateYield 81.8%

Procedure

To a solution of 5-amino-2-fluorobenzoic acid (89.6 g, 577 mmol) in MeOH (1000 mL) was added sulfurous dichloride (82.4 g, 692 mmol) dropwise at 0° C. Then the mixture was heated to reflux for overnight. The solvent was removed. The residue was diluted with EtOAc (1 L). Then the pH was adjusted to around 9 by progressively adding saturated NaHCO3. The organic layer was separated. The aqueous layer was extracted with EtOAc (500 L×3). The combined organic layers were washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound of step A (79.8 g, 81.8% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.16-7.20 (m, 1H), 6.90-6.98 (m, 1H), 6.75-6.82 (m, 1H), 3.89 (s, 3H), 3.51-3.70 (br, 2H).

Workup

  1. temperatureThen the mixture was heated
  2. temperatureto reflux for overnight
  3. customThe solvent was removed
  4. additionThe residue was diluted with EtOAc (1 L)
  5. customThe organic layer was separated
  6. extractionThe aqueous layer was extracted with EtOAc (500 L×3)
  7. washThe combined organic layers were washed with water and brine successively
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ec0c6808cddf4126b4202b982b4d3c33
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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