Acetic Acid → Methyl 2-fluoro-4-(methylamino)benzoate

HRID 2252054Notes

Reaction equation

HRID 2252054 reaction equation
C=O.[CH3:3][O:4][C:5](=[O:14])[C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][C:7]=1[F:13].[C:15](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:3][O:4][C:5](=[O:14])[C:6]1[CH:11]=[CH:10][C:9]([NH:12][CH3:15])=[CH:8][C:7]=1[F:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 21957875Methyl 4-amino-2-fluorobenzoate

Product 1

HCID 69208619Methyl 2-fluoro-4-(methylamino)benzoateYield 15%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Add formaldehyde (0.15 g) to a mixture of 2-fluoro-4-amino benzoic acid methyl ester (0.62 g), acetic acid (2.1 mL) and 1,2 dichloroethane (20 mL). Stir at room temperature overnight. Add sodium triacetoxyborohydride (1.15 g) and stir at room temperature for 2 hours. Quench by pouring the reaction mixture into a mixture of saturated aqueous sodium bicarbonate and ethyl acetate. Separate the layers, wash the organic phase with water, dry the remaining organic phase over sodium sulfate and then concentrate under reduced pressure. The residue is purified by chromatography eluting with ethyl acetate:hexane (1:4) to provide 2-fluoro-4-methylamino benzoic acid methyl ester (0.10 g, 15%) as an oil.

Workup

  1. customQuench
  2. additionby pouring the reaction mixture
  3. additioninto a mixture of saturated aqueous sodium bicarbonate and ethyl acetate
  4. customSeparate the layers
  5. washwash the organic phase with water
  6. dry with materialdry the remaining organic phase over sodium sulfate
  7. concentrationconcentrate under reduced pressure
  8. customThe residue is purified by chromatography
  9. washeluting with ethyl acetate:hexane (1:4)

Sources & evidence

ORD record
ord-85c43cee300c41108dccd6b26e5b09d7
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

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