2,2,2-Trifluoroethanol → HCID 178516590, compound

HRID 2405829Notes

Reaction equation

HRID 2405829 reaction equation
[H-].[Na+].[CH2:3]([OH:8])[C:4]([F:7])([F:6])[F:5].[Cl:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[C:17](S(CC)(=O)=O)[CH:16]=[C:15]2[O:25]CC1C=CC(OC)=CC=1.N1C2C(=CC=CC=2)C=CC=1>C1COCC1.C(Cl)Cl.FC(F)(F)C(O)=O>[Cl:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[C:17]([O:8][CH2:3][C:4]([F:7])([F:6])[F:5])[CH:16]=[C:15]2[OH:25]

Participants

8

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 7047QuinolineHCID 24758Sodium hydrideHCID 59379041HCID 59379041, compound

Product 1

HCID 178516590HCID 178516590, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of sodium hydride (60 wt %, 177 mg, 7.7 mmol) in THF (3 mL) was added trifluoroethanol and 8-chloro-2-ethanesulfonyl-4-(4-methoxy-benzyloxy)-quinoline (300 mg, 0.77 mmol). The reaction was stirred at room temperature for 1 h, quenched with H2O, then diluted with EtOAc and washed with brine. The resulting organic layer was dried over sodium sulfate and concentrated to provide crude 8-Chloro-4-(4-methoxy-benzyloxy)-2-(2,2,2-trifluoro-ethoxy)-quinoline. LCMS found 397.9 [M+H]+. The crude quinoline was then dissolved in CH2Cl2 (4 mL) and trifluoroacetic acid (4 mL). After stirring for 15 min the reaction was concentrated. The crude product was purified by column chromatography (10→30% EtOAc/hexanes) to provide 8-chloro-2-(2,2,2-trifluoro-ethoxy)-quinolin-4-ol (220 mg, 100% yield). LCMS found 278.3 [M+H]+.

Workup

  1. customquenched with H2O
  2. additiondiluted with EtOAc
  3. washwashed with brine
  4. dry with materialThe resulting organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customto provide crude 8-Chloro-4-(4-methoxy-benzyloxy)-2-(2,2,2-trifluoro-ethoxy)-quinoline
  7. stirringAfter stirring for 15 min the reaction
  8. concentrationwas concentrated
  9. customThe crude product was purified by column chromatography (10→30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e7e6f88997ae430db595f23f455e524e
Source dataset
uspto-grants-2014_08
Patent number
US08809267B2

Reaction notes

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