2,2,2-Trifluoroethanol → HCID 86682930, compound

HRID 1497055Notes

Reaction equation

HRID 1497055 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].[CH2:9]([O:11][C:12]([C:14]1[C:15](Cl)=[N:16][C:17]2[C:22]([C:23]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:21][C:20]([Cl:30])=[CH:19][CH:18]=2)=[O:13])[CH3:10]>CN(C=O)C>[CH2:9]([O:11][C:12]([C:14]1[C:15]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[N:16][C:17]2[C:22]([C:23]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:21][C:20]([Cl:30])=[CH:19][CH:18]=2)=[O:13])[CH3:10]

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 1714247Ethyl 2,6-dichloro-4-phenylquinoline-3-carboxylate

Product 1

HCID 86682930HCID 86682930, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To the stirred solution of 2,2,2-trifluoro-ethanol (0.051 ml, 0.69 mmol) in 4 ml of DMF, was added NaH (28 mg, 0.69 mmol) portion wise at 0° C. The mixture was stirred for 30 min at room temperature and then a solution of 2,6-dichloro-4-phenyl-quinoline-3-carboxylic acid ethyl ester (200 mg, 0.58 mmol) in 2 ml dry DMF was added. The resulting reaction mixture was stirred for 5 h at room temperature. The reaction mixture was quenched with saturated aqueous NH4Cl solution and then diluted with further water, and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give a crude residue which was purified by flash column chromatography (5% ethyl acetate in hexane) to obtain 6-chloro-4-phenyl-2-(2,2,2-trifluoro-ethoxy)-quinoline-3-carboxylic acid ethyl ester (140 mg, 59%) as off white solid. LC-MS: 410 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred for 5 h at room temperature
  3. customThe reaction mixture was quenched with saturated aqueous NH4Cl solution
  4. additiondiluted with further water
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto give a crude residue which
  10. customwas purified by flash column chromatography (5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f08c63f92686491f87f7e3e9eda06928
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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