Toluene → Benzaldehyde, 4-[ethyl[2-[(tetrahydro-2H-pyran-2-yl)oxy]ethyl]amino]-

HRID 356225Notes

Reaction equation

HRID 356225 reaction equation
[CH2:1]([N:3]([CH2:11][CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1)[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1)[CH3:2].C1(C)C=CC=CC=1.C([Li])(C)(C)C.C1C[O:35][CH2:34]C1>O.CN(C)C=O.CCCCC>[CH2:1]([N:3]([CH2:11][CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1)[C:4]1[CH:9]=[CH:8][C:7]([CH:34]=[O:35])=[CH:6][CH:5]=1)[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 18941483N-ethyl-N-[2-(tetrahydropyran-2-yl)oxyethyl]-4-bromoanilineHCID 178418306HCID 178418306, compound

Product 1

HCID 10880399Benzaldehyde, 4-[ethyl[2-[(tetrahydro-2H-pyran-2-yl)oxy]ethyl]amino]-Yield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8003PentaneSolvent

Conditions

Temperature
-78 °C

Procedure

Water content in 45.1 g (0.14 mol) of N-ethyl-N-[2-(tetrahydropyran-2-yl)oxyethyl]-4-bromoaniline was removed by azeotropic distillation carried out twice with toluene, followed by dissolution in 390 ml of anhydrous THF in an atmosphere of argon. The solution obtained was cooled to -78° C., and 195 ml (2.2-fold equivalent weight) of t-butyllithium (1.55M, an n-pentane solution) was dropwise added thereto, followed by stirring for 45 minutes. To the resulting reaction solution, 23 ml of N,N-dimethylformamide (hereinafter "DMF") was added, and the mixture obtained was stirred at room temperature for 5 hours. Thereafter, 100 ml of water was added to the resulting solution, which was then extracted with chloroform (100 ml×3). The organic layer obtained was dried with anhydrous sodium sulfate and then concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (developing system: hexane/ethyl acetate=2/1) to obtain 35.0 g of N-ethyl-N-[2-(tetrahydropyran-2-yl)oxyethyl]-4-formylaniline (yield: 92%).

Workup

  1. customThe solution obtained
  2. additionwas added
  3. customthe mixture obtained
  4. stirringwas stirred at room temperature for 5 hours
  5. extractionwas then extracted with chloroform (100 ml×3)
  6. customThe organic layer obtained
  7. dry with materialwas dried with anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by silica gel column chromatography (developing system: hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-c7879fb6389940b8a571970e89802c20
Source dataset
uspto-grants-1998_11
Patent number
US05834575

Reaction notes

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