Trifluoroacetic acid → HCID 86650870, compound

HRID 1967566Notes

Reaction equation

HRID 1967566 reaction equation
FC(F)(F)C(O)=O.FC(F)(F)C1C=CC(N2[C@@H](C3C=CC=C(OC(F)(F)F)C=3)C=C(N[C@@H](C3C=CC(Cl)=CC=3)C)C2=O)=CC=1.[F:45][C:46]([F:72])([F:71])[O:47][C:48]1[CH:49]=[C:50]([C@@H:54]2[N:58]([C:59]3[CH:64]=[CH:63][C:62]([C:65]([F:68])([F:67])[F:66])=[CH:61][CH:60]=3)[C:57](=[O:69])[C:56](=O)[CH2:55]2)[CH:51]=[CH:52][CH:53]=1.[CH3:73][C:74]([NH2:86])([C:76]1[CH:81]=[CH:80][N:79]=[C:78]([C:82]([F:85])([F:84])[F:83])[N:77]=1)[CH3:75]>C(O)(=O)C.O.C1(C)C=CC=CC=1>[CH3:75][C:74]([NH:86][C:56]1[C:57](=[O:69])[N:58]([C:59]2[CH:64]=[CH:63][C:62]([C:65]([F:66])([F:68])[F:67])=[CH:61][CH:60]=2)[C@@H:54]([C:50]2[CH:51]=[CH:52][CH:53]=[C:48]([O:47][C:46]([F:72])([F:45])[F:71])[CH:49]=2)[CH:55]=1)([C:76]1[CH:81]=[CH:80][N:79]=[C:78]([C:82]([F:83])([F:85])[F:84])[N:77]=1)[CH3:73]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24984347HCID 24984347, compoundHCID 58138257HCID 58138257, compoundHCID 86638167HCID 86638167, compound2×

Product 1

HCID 86650870HCID 86650870, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Procedure

Add trifluoroacetic acid (7.56 mL, 100 mmol) to a solution of 1-(4-trifluoromethyl-phenyl)-3-[(R)-1-(4-chloro-phenyl)-ethylamino]-5(R)-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (10.8 g, 20.0 mmol) in acetic acid (100 mL) and water (5 mL). Stir at ambient temperature for 60 min. Observe significant formation of (R)-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione (LC-MS ESI m/z: 426 (M+Na)+, Tr=2.76 min., method 2). Dilute the reaction with toluene (200 mL) and water (150 mL). Wash the organic layer with water and saturated aqueous sodium bicarbonate solution. Filter the organic layer through sodium sulfate. Add acetic acid (9.17 mL, 160 mmol) and 1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamine (4.51 g, 22 mmol) to this toluene solution containing (R)-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione. Heat to 55° C. for 18 hours. Concentrate reaction mixture under reduced pressure to give a dark purple oil. Purify the residue by silica gel chromatography (25% ethyl acetate-hexane) to obtain (R)-3-[1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamino]-1-(4-trifluoromethyl-phenyl)-5-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (7.70 g, 65%) as a purple foam. LC-MS ESI m/z: 613 (M+Na)+, Tr=3.35 min., method 2.

Workup

  1. additionDilute
  2. washWash the organic layer with water and saturated aqueous sodium bicarbonate solution
  3. filtrationFilter the organic layer through sodium sulfate
  4. temperatureHeat to 55° C. for 18 hours
  5. concentrationConcentrate
  6. customreaction mixture under reduced pressure
  7. customto give a dark purple oil
  8. customPurify the residue by silica gel chromatography (25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-7f893755190d45cfa62b92fc34faf236
Source dataset
uspto-grants-2013_04
Patent number
US08420654B2

Reaction notes

Loading…