Tetrafluoroboric acid → 3-Fluoro-5-hydroxy-4-methoxybenzoic acid

HRID 2094686Notes

Reaction equation

HRID 2094686 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12](N)[C:13]=1[O:14][CH3:15])[C:8]([OH:10])=[O:9])(=O)C.N([O-])=O.[Na+].[F:21][B-](F)(F)F.[H+]>>[F:21][C:12]1[CH:11]=[C:7]([CH:6]=[C:5]([OH:4])[C:13]=1[O:14][CH3:15])[C:8]([OH:10])=[O:9]

Participants

4

Reactant 3

HCID 28118Tetrafluoroboric acidHCID 129240263-Acetoxy-5-amino-4-methoxy-benzoic acidHCID 23668193Sodium Nitrite

Product 1

HCID 670765923-Fluoro-5-hydroxy-4-methoxybenzoic acid

Procedure

The compound of step 1 (2.0 g, 8.88 mmol) was dissolved in aqueous tetrafluoroboric acid (48%, 4.5 ml), sodium nitrite (612 mg, 8.88 mmol) was added at 0° C., and the mixture was stirred at room temperature for 60 min. The volatiles were evaporated, toluene was added to the oily residue and the mixture was heated at 100° C. for 4 h. The mixture was partitioned between EA and 2 N hydrochloric acid, the aqueous phase extracted with EA, and the combined organic extracts were dried over sodium chloride, decanted and evaporated to dryness. The residue was purified by preparative RP HPLC (water/ACN gradient) to give 170 mg of the title compound.

Workup

  1. customThe volatiles were evaporated
  2. additiontoluene was added to the oily residue
  3. temperaturethe mixture was heated at 100° C. for 4 h
  4. customThe mixture was partitioned between EA and 2 N hydrochloric acid
  5. extractionthe aqueous phase extracted with EA
  6. dry with materialthe combined organic extracts were dried over sodium chloride
  7. customdecanted
  8. customevaporated to dryness
  9. customThe residue was purified by preparative RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-962af8cd4eef4cb291e73aa32b4e98cf
Source dataset
uspto-grants-2013_05
Patent number
US08445530B2

Reaction notes

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