Tetrahydrofuran → HCID 66779076, compound

HRID 2091093Notes

Reaction equation

HRID 2091093 reaction equation
[CH2:1]([CH:3]([CH2:27][CH3:28])[CH:4]([NH:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[CH:19][CH:18]=1)[C:5]1[O:6][C:7]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:8]=2[C:9]=1[CH3:10])[CH3:2].O1CCCC1.[OH-].[Na+]>C(O)C>[CH2:27]([CH:3]([CH2:1][CH3:2])[CH:4]([NH:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]([OH:23])=[O:22])=[CH:25][CH:26]=1)[C:5]1[O:6][C:7]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:8]=2[C:9]=1[CH3:10])[CH3:28]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium Hydroxide3×HCID 66777975HCID 66777975, compound

Product 1

HCID 66779076HCID 66779076, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a mixture of methyl 4-{[2-ethyl-1-(5-fluoro-3-methyl-1-benzofuran-2-yl)butyl]amino}benzoate (709 mg) synthesized above, tetrahydrofuran (6 mL) and ethanol (6 mL) was added 1N aqueous sodium hydroxide solution (3.7 mL), and the mixture was heated under reflux for 14 hr. 1N Aqueous sodium hydroxide solution (4.0 mL) was added, and the mixture was further stirred with heating under reflux for 2 hr. 8N Aqueous sodium hydroxide solution (2.0 mL) and ethanol (2 mL) were added to the mixture, and the mixture was further stirred with heating under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure, 8N aqueous sodium hydroxide solution (4.0 mL), ethanol (4 mL) and tetrahydrofuran (4 mL) were added, and the mixture was further stirred with heating under reflux for 1 hr. The reaction mixture was allowed to cool to room temperature, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate 100:0-70:30, v/v) to give the title compound (412 mg, 61%) as a colorless amorphous form.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 14 hr
  3. temperaturewith heating
  4. temperatureunder reflux for 2 hr
  5. stirringthe mixture was further stirred
  6. temperaturewith heating
  7. temperatureunder reflux for 1 hr
  8. concentrationThe reaction mixture was concentrated under reduced pressure, 8N aqueous sodium hydroxide solution (4.0 mL), ethanol (4 mL) and tetrahydrofuran (4 mL)
  9. additionwere added
  10. stirringthe mixture was further stirred
  11. temperaturewith heating
  12. temperatureunder reflux for 1 hr
  13. addition1N hydrochloric acid was added
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe extract was washed with saturated brine
  16. dry with materialdried over magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate 100:0-70:30, v/v)

Sources & evidence

ORD record
ord-eb699e69f375452db0899a259fde80b4
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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