Sodium hydride → HCID 70873649, compound

HRID 2172227Notes

Reaction equation

HRID 2172227 reaction equation
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][OH:11])=[CH:6][CH:5]=1.[H-].[Na+].Cl[C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[CH:23]=2)[N:18]=1.[Cl-].[NH4+]>CN(C=O)C>[O:29]1[CH2:30][CH2:31][CH2:32][CH2:33][CH:28]1[O:27][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([O:11][CH2:10][C:7]1[CH:6]=[CH:5][C:4]([O:3][C:2]([F:12])([F:13])[F:1])=[CH:9][CH:8]=1)[CH:26]=[CH:25]2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1371844-(Trifluoromethoxy)benzenemethanolHCID 86709380HCID 86709380, compound

Product 1

HCID 70873649HCID 70873649, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (4-(trifluoromethoxy)phenyl)methanol (1.65 ml, 11.4 mmol) in DMF (40 ml) was added 60% sodium hydride (0.46 g, 11.4 mmol) at 0° C. and further stirred for 20 minutes. While stirring the resulting mixture under ice cooling, 2-chloro-6-(tetrahydropyran-2-yloxy)-quinoline (3.0 g, 11.4 mmol) was added thereto and warmed to room temperature, followed by further stirring for 5 hours. A saturated ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and then dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=80:20). The resulting crude crystal was washed with hexane-diethylether to afford the title compound as a white powder (3.84 g, yield 81%).

Workup

  1. stirringWhile stirring the resulting mixture under ice cooling
  2. stirringby further stirring for 5 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtering
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by silica gel column chromatography (hexane:ethyl acetate=80:20)
  10. washThe resulting crude crystal was washed with hexane-diethylether

Sources & evidence

ORD record
ord-f41426de5cf6434fbe99813dc3f14e5b
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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