Aniline → 2-(4-Tert-butyl-benzenesulfonylamino)-4-fluoro-benzoic acid

HRID 2238293Notes

Reaction equation

HRID 2238293 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C(=O)(O)[O-].[Na+].[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18].NC1C=CC=CC=1>O.O1CCOCC1>[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:1][C:2]2[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 6115AnilineHCID 1398824-t-Butylbenzenesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 27249674-Fluoroanthranilic acid

Product 1

HCID 452998872-(4-Tert-butyl-benzenesulfonylamino)-4-fluoro-benzoic acidYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Amino-4-fluorobenzoic acid (25 g 161 mmol) was added to a solution of sodium bicarbonate (54.1 g, 645 mmol) in water (2.4 L) at room temperature and was stirred until homogeneous. The resultant solution was heated to 60° C. in an oil bath. 4-tert-Butylbenzenesulfonyl chloride (45.0 g 193 mmol), dissolved in 200 mL p-dioxane, was subsequently added dropwise to the stirring aniline solution in a steady stream over a 30 min period. The reaction mixture was stirred at 60° C. overnight. The following day, upon LCMS verification of consumption of the aniline, the solution was poured in a slow stream into one liter of rapidly stirring 2 M HCl/H2O. The resultant precipitate was collected by vacuum filtration, washed thoroughly with water, and dried in vacuo to afford 46 g of 2-(4-tert-butyl-benzenesulfonylamino)-4-fluoro-benzoic acid as an off-white solid (82% yield): HPLC retention time=2.68; MS (ES) M+H expected 352.0, found 352.0.

Workup

  1. stirringThe reaction mixture was stirred at 60° C. overnight
  2. customThe following day, upon LCMS verification of consumption of the aniline
  3. additionthe solution was poured in a slow stream into one liter
  4. stirringof rapidly stirring 2 M HCl/H2O
  5. filtrationThe resultant precipitate was collected by vacuum filtration
  6. washwashed thoroughly with water
  7. customdried in vacuo

Sources & evidence

ORD record
ord-7c560d09ebea4d2a82685fde591fcdd5
Source dataset
uspto-grants-2010_05
Patent number
US07718683B2

Reaction notes

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