Hydrochloric Acid → HCID 63183789, compound

HRID 2277188Notes

Reaction equation

HRID 2277188 reaction equation
[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[F:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([F:19])[C:17]=1F)[C:12]([OH:14])=[O:13].Cl>CN(C=O)C>[CH:1]1([CH2:4][O:5][C:17]2[C:16]([F:19])=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=2[F:8])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 8531543,4,5-Trifluorobenzoic acid

Product 1

HCID 63183789HCID 63183789, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of cyclopropylmethanol (5.62 mL) in DMF (30 mL) was added sodium hydride (60% oil, 2.84 g), and the mixture was stirred at room temperature for 15 min. To the reaction mixture was added 3,4,5-trifluorobenzoic acid (5.00 g), and the mixture was stirred at room temperature for 30 min. The reaction mixture was neutralized with 6 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in DMF (20 mL) were added potassium carbonate (3.92 g) and methyl iodide (1.77 mL), and the mixture was stirred with heating at 60° C. for 40 min. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained oil in a mixed solvent of THF (20 mL) and methanol (20 mL) was added 2 M aqueous sodium hydroxide solution (28.8 mL), and the mixture was stirred with heating at 60° C. for 40 min. The reaction mixture was allowed to cool to room temperature, and neutralized with 6 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid was washed with hexane to give the title compound (5.32 g).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe obtained organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. additionTo a solution of the obtained residue in DMF (20 mL) were added potassium carbonate (3.92 g) and methyl iodide (1.77 mL)
  7. stirringthe mixture was stirred
  8. temperaturewith heating at 60° C. for 40 min
  9. temperatureto cool to room temperature
  10. additiondiluted with ethyl acetate
  11. washwashed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  15. additionTo a solution of the obtained oil in a mixed solvent of THF (20 mL) and methanol (20 mL) was added 2 M aqueous sodium hydroxide solution (28.8 mL)
  16. stirringthe mixture was stirred
  17. temperaturewith heating at 60° C. for 40 min
  18. temperatureto cool to room temperature
  19. extractionthe mixture was extracted with ethyl acetate
  20. washThe obtained organic layer was washed with saturated brine
  21. dry with materialdried over anhydrous magnesium sulfate
  22. customthe solvent was evaporated under reduced pressure
  23. washThe obtained solid was washed with hexane

Sources & evidence

ORD record
ord-a2b98d1930f844458d1c685da632fa97
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

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