Sodium Hydroxide → 4,4,4-Trifluoro-3-(phenylamino)butanoic acid

HRID 418704Notes

Reaction equation

HRID 418704 reaction equation
[F:1][C:2]([F:23])([F:22])[CH:3]([CH:11](C(OCC)=O)[C:12]([O:14]CC)=[O:13])[NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[OH-].[Na+]>O.C(O)C>[F:1][C:2]([F:22])([F:23])[CH:3]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:11][C:12]([OH:14])=[O:13]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 12990241Diethyl 2-(2,2,2-trifluoro-1-(phenylamino)ethyl)malonate

Product 1

HCID 129902464,4,4-Trifluoro-3-(phenylamino)butanoic acidYield 13.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of compound 326 (2.16 g, 6.48 mmol) and sodium hydroxide (2.60 g, 64.8 mmol) in water (5.2 mL) and ethanol (26 mL) was stirred at room temperature for 24 h. The solvents were removed under reduced pressure leaving a white solid which was triturated in ether, isolated by filtration, rinsed with ether and dried under high vacuum. The white solid was dissolved in water (12 mL), and the solution was neutralized to pH 4 with a 3N HCl solution, extracted twice with EtOAc, the combined organic layers were dried over sodium sulfate and the solvent removed under reduced pressure. The solid was dissolved in dry toluene (20 mL), heated to reflux for 1 h with continuous stirring, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent EtOAc-hexane, gradient 0:100 to 40:60) to afford title compound 327 (204 mg, 0.87 mmol, 13% yield) as a beige solid. 1H NMR (400 MHz, CDCl3) δ ppm: 7.24-7.18 (m, 2H), 6.82 (tt, J=7.2, 1.0 Hz, 1H), 6.75-6.71 (m, 2H), 4.55-4.45 (m, 1H), 2.89 (dd, J=16.0, 4.4 Hz, 1H), 2.67 (dd, J=16.0, 8.8 Hz, 1H). LRMS (M−1) 231.9 (100%).

Workup

  1. customThe solvents were removed under reduced pressure
  2. customleaving a white solid which
  3. customwas triturated in ether
  4. customisolated by filtration
  5. washrinsed with ether
  6. customdried under high vacuum
  7. dissolutionThe white solid was dissolved in water (12 mL)
  8. extractionextracted twice with EtOAc
  9. dry with materialthe combined organic layers were dried over sodium sulfate
  10. customthe solvent removed under reduced pressure
  11. dissolutionThe solid was dissolved in dry toluene (20 mL)
  12. temperatureheated
  13. temperatureto reflux for 1 h with continuous stirring
  14. customthe solvent was removed under reduced pressure
  15. customThe residue was purified by column chromatography on silica gel (eluent EtOAc-hexane, gradient 0:100 to 40:60)

Sources & evidence

ORD record
ord-69bcaa285e6146aba781219832c91d59
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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