Hydrochloric Acid → 2-(6-acetamidochroman-2-yl)acetic Acid

HRID 1071189Notes

Reaction equation

HRID 1071189 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][CH:10]([CH2:15][C:16]([O:18]CC)=[O:17])[CH2:9][CH2:8]2)(=[O:3])[CH3:2].CO.[OH-].[Na+].Cl>C(=O)(O)[O-].[Na+]>[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][CH:10]([CH2:15][C:16]([OH:18])=[O:17])[CH2:9][CH2:8]2)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 11391771HCID 11391771, compound

Product 1

HCID 114366002-(6-acetamidochroman-2-yl)acetic Acid

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

To the dark brown ethyl 6-acetamidochroman-2-ylacetate of Example 5 was added 3.5 L of methanol and 3.5 L of 1 N aqueous sodium hydroxide. After stirring the reaction mixture for 2 h at room temperature, the methanol was removed from the reaction mixture providing a dark, aqueous residue. The residue was transferred into a separatory funnel and extracted with 3×2 L of methylene chloride. Between each extraction step, the aqueous fraction was distilled to remove any organic solvent. The pH of the aqueous fraction was adjusted to about 2 with 2 N hydrochloric acid, affording a sticky, dark oil, which was separated. The acidic, aqueous fraction was extracted with 3×2 L of ethyl acetate. The ethyl acetate extracts and the dark oil were combined to form a homogenous solution. This solution was washed 2×2 L of brine and dried over 100 g of anhydrous sodium sulfate. Removing the ethyl acetate afforded a thick, blackish oil, which solidified overnight under vacuum. The dark brown solid was dissolved in saturated aqueous sodium bicarbonate to provide a black solution. The well-stirred, black solution was titrated with 3 N hydrochloric acid. At about pH 7.5, a black oil began to form on the walls of the flask. At about pH 7.0, more black oil formed, and the color of the solution changed from black to light yellow. The mixture was allowed to stand for about 5 min for the black oil to settle. The supernatant was decanted and acidified to about pH 2.0. The resulting white suspension was stirred for 30 min. The precipitate was filtered and dried at 50° C. under reduced pressure affording 350 g of 2-(6-acetamidochroman-2-yl)acetic acid as off-white crystals. The overall yield from 1347 g of 6-(tert-butyloxycarbonylamino)chroman-2-one from example 1 was 46.2%.

Workup

  1. customthe methanol was removed from the reaction mixture
  2. customproviding a dark, aqueous residue
  3. customThe residue was transferred into a separatory funnel
  4. extractionextracted with 3×2 L of methylene chloride
  5. extractionBetween each extraction step
  6. distillationthe aqueous fraction was distilled
  7. customto remove any organic solvent
  8. customaffording a sticky, dark oil, which
  9. customwas separated
  10. extractionThe acidic, aqueous fraction was extracted with 3×2 L of ethyl acetate
  11. customto form a homogenous solution
  12. washThis solution was washed 2×2 L of brine
  13. dry with materialdried over 100 g of anhydrous sodium sulfate
  14. customRemoving the ethyl acetate
  15. customafforded a thick, blackish oil, which
  16. waitsolidified overnight under vacuum
  17. customto provide a black solution
  18. customto form on the walls of the flask
  19. customAt about pH 7.0, more black oil formed
  20. waitto stand for about 5 min for the black oil
  21. customThe supernatant was decanted
  22. stirringThe resulting white suspension was stirred for 30 min
  23. filtrationThe precipitate was filtered
  24. customdried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-a0cf9cec9d7f47cdbc981d4e53ca747e
Source dataset
uspto-grants-2005_06
Patent number
US06903227B2

Reaction notes

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