Sodium Hydroxide → 4,4,4-trifluoro-3-[(R)-2-(3-trifluoromethylphenyl)-morpholin-4-ylmethyl]-butyric acid

HRID 530633Notes

Reaction equation

HRID 530633 reaction equation
C([O:3][C:4](=[O:28])[CH2:5][CH:6]([CH2:11][N:12]1[CH2:17][CH2:16][O:15][C@H:14]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[CH2:13]1)[C:7]([F:10])([F:9])[F:8])C.[OH-].[Na+]>C(O)C>[F:10][C:7]([F:8])([F:9])[CH:6]([CH2:11][N:12]1[CH2:17][CH2:16][O:15][C@H:14]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=2)[CH2:13]1)[CH2:5][C:4]([OH:28])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 1178708034,4,4-trifluoro-3-[(R)-2-(3-trifluoromethyl-phenyl)-morpholin-4-ylmethyl]-butyric acid ethyl ester

Product 1

HCID 1178707014,4,4-trifluoro-3-[(R)-2-(3-trifluoromethylphenyl)-morpholin-4-ylmethyl]-butyric acidYield 100.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 0.589 g (1.4 mmol) of 4,4,4-trifluoro-3-[(R)-2-(3-trifluoromethyl-phenyl)-morpholin-4-ylmethyl]-butyric acid ethyl ester, ca. 1.07 mL of 2 M sodium hydroxide solution and 14 mL of ethanol was heated at reflux and stirred under an atmosphere of argon. After 25 min, volatiles were removed under reduced pressure. The mixture was treated with 40 mL of saturated sodium dihydrogen phosphate solution, and extracted twice with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.543 g (99%) of 4,4,4-trifluoro-3-[(R)-2-(3-trifluoromethylphenyl)-morpholin-4-ylmethyl]-butyric acid as a glass. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.10-2.21 (m, 1H) 2.31-2.66 (m, 3H overlapping DMSO) 2.79 (dd, J=16.81, 11.54 Hz, 1H) 2.95-3.21 (m, 2H) 3.34 (s, 2H) 3.65 (dtd, J=18.23, 11.34, 11.34, 2.26 Hz, 1H) 3.91-4.02 (m, 1H) 4.45-4.64 (m, 1H) 7.53-7.75 (m, 4H) 12.49 (br. s., 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. customvolatiles were removed under reduced pressure
  4. additionThe mixture was treated with 40 mL of saturated sodium dihydrogen phosphate solution
  5. extractionextracted twice with ethyl acetate
  6. washThe combined ethyl acetate layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e0d0f59b097746ff9fa037014237c243
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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