Trifluoroacetic acid → 2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazole

HRID 1964497Notes

Reaction equation

HRID 1964497 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:40])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[N:24](C(OC(C)(C)C)=O)[C:25]([C:28]3[S:29][CH:30]=[CH:31][N:32]=3)=[CH:26][CH:27]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[CH:11]=1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][CH2:3][C@H:4]([CH3:40])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:24][C:25]([C:28]3[S:29][CH:30]=[CH:31][N:32]=3)=[CH:26][CH:27]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:20])=[O:21])=[CH:15][CH:14]=2)[CH:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66682326t-Butyl 2-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

Product 1

HCID 580654642-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazoleYield 88.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

t-Butyl 2-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (7.16 g, 12.2 mmol) synthesized in Example (1h) was dissolved in dichloromethane (15 mL), and cooled to 0° C. Trifluoroacetic acid (30 mL) was added dropwise with stirring under nitrogen atmosphere. Stirring was carried out at room temperature for 30 minutes, followed by further stirring at 40° C. for 30 minutes. The solvent was distilled off under reduced pressure followed by dilution with ethyl acetate (300 mL), a saturated aqueous sodium hydrogencarbonate solution (200 mL) was added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-50%) to afford the desired compound (5.21 g, yield 88%) as a pale yellow solid.

Workup

  1. stirringStirring
  2. stirringby further stirring at 40° C. for 30 minutes
  3. distillationThe solvent was distilled off under reduced pressure
  4. additiona saturated aqueous sodium hydrogencarbonate solution (200 mL) was added
  5. customthe solution was separated
  6. washThe organic layer was washed with saturated brine
  7. dry with materialsubsequently dried over sodium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe resulting residue was purified
  10. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-50%)

Sources & evidence

ORD record
ord-d97e124ea9d84208a664df5a078a5618
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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