Trifluoroacetic acid → HCID 57951195, compound

HRID 1919795Notes

Reaction equation

HRID 1919795 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.[F:8][C:9]([F:45])([F:44])[O:10][C:11]1[CH:12]=[C:13]([CH:17]2[N:21]([C:22]3[CH:27]=[CH:26]C(C(F)(F)F)=[CH:24][CH:23]=3)[C:20](=[O:32])[C:19](NC3C=CC(C(F)(F)F)=CC=3)=[CH:18]2)[CH:14]=[CH:15][CH:16]=1.C[O:47]C1CCC(OC)O1>O.C(O)(=O)C.C(O)C>[OH:47][C:19]1[C:20](=[O:32])[N:21]([C:22]2[CH:27]=[CH:26][C:3]([C:2]([F:7])([F:6])[F:1])=[CH:24][CH:23]=2)[CH:17]([C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([O:10][C:9]([F:8])([F:45])[F:44])[CH:12]=2)[CH:18]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 790982,5-DimethoxytetrahydrofuranHCID 58129475HCID 58129475, compound

Product 1

HCID 57951195HCID 57951195, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

Mix ethanol (120 mL), glacial acetic acid (15 mL), water (3.0 mL, 164.7 mmol), trifluoroacetic acid (6.2 mL, 82.4 mmol), (±)-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-3-(4-trifluoromethyl-phenylamino)-1,5-dihydro-pyrrol-2-one (30.0 g, 54.9 mmol), and 2,5-dimethoxy-tetrahydrofuran (10.7 mL, 82.4 mmol). Warm the solution to 50° C. and stir the reaction mixture for 15-18 hours. Discontinue heating the solution, add water (35 mL), and cool the reaction mixture to −19° C. Filter the slurry and wash the solid with a 1:4 mixture of water-methanol (20 mL). Transfer the filtrate to a separatory funnel and wash with 6% brine (280 mL), then add 6% brine (100 mL), methanol (40 mL), diethyl ether (100 mL), and saturated sodium bicarbonate solution (43 mL) to the organic phase. Separate the layers, add methanol (60 mL) to the organic phase, and concentrate the solution to approximately 1 volume containing (±)-3-hydroxy-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-1,5-dihydro-pyrrol-2-one.

Workup

  1. temperatureDiscontinue heating the solution
  2. temperaturecool the reaction mixture to −19° C
  3. filtrationFilter the slurry
  4. washwash the solid
  5. additionwith a 1:4 mixture of water-methanol (20 mL)
  6. washTransfer the filtrate to a separatory funnel and wash with 6% brine (280 mL)
  7. additionadd 6% brine (100 mL), methanol (40 mL), diethyl ether (100 mL), and saturated sodium bicarbonate solution (43 mL) to the organic phase
  8. customSeparate the layers
  9. additionadd methanol (60 mL) to the organic phase
  10. concentrationconcentrate the solution to approximately 1 volume
  11. additioncontaining (±)-3-hydroxy-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-1,5-dihydro-pyrrol-2-one

Sources & evidence

ORD record
ord-4905867aa72b4000b294be5dd29750a1
Source dataset
uspto-grants-2012_05
Patent number
US08168659B2

Reaction notes

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