Dimethylformamide → N-ethyl-N-[6-(tetrahydropyran-2-yl)oxyhexyl]-4-formylaniline

HRID 1004778Notes

Reaction equation

HRID 1004778 reaction equation
[CH2:1]([N:3]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1)[CH3:2].C([Li])(C)(C)C.CN(C)[CH:31]=[O:32]>O1CCCC1>[CH2:1]([N:3]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[C:4]1[CH:9]=[CH:8][C:7]([CH:31]=[O:32])=[CH:6][CH:5]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 18793549N-ethyl-N-[6-(tetrahydropyran-2-yl)oxyhexyl]-4-bromoanilineHCID 178418306HCID 178418306, compound

Product 1

HCID 18793531N-ethyl-N-[6-(tetrahydropyran-2-yl)oxyhexyl]-4-formylanilineYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

50.0 g (130 mmols) of N-ethyl-N-[6-(tetrahydropyran-2-yl)oxyhexyl]-4-bromoaniline was dissolved in 180 ml of anhydrous tetrahydrofuran in an atmosphere of argon, and the solution obtained was cooled to -78° C. To the reaction solution obtained, 174.4 ml (2.2-fold equivalent weight) of t-butyl lithium (1.64 M, n-pentane solution) was dropwise added, followed by stirring for 1 hour. To the mixture obtained, 12.3 g (1.3-fold equivalent weight) of N,N-dimethylformamide was dropwise added, which was then stirred at room temperature for 2 hours and 30 minutes. The resultant reaction solution was concentrated, and dissolved in 500 ml of ethyl acetate, followed by washing twice with 300 ml of water. The organic layer thus formed was dried with anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (developing system: hexane/ethyl acetate=4/1) to obtain 34.7 g of N-ethyl-N-[6-(tetrahydropyran-2-yl)oxyhexyl]-4-formylaniline (yield: 80%; a pale-yellow oily liquid). 1H-NMR Spectrum [δ(ppm)]: 1.20(t, 3H, J=7.0 Hz), 1.35-1.95(m, 14H), 3.20-3.55(m, 6H), 3.73(m, 1H), 3.86(m, 1H), 4.57(t, 1H, J=3.6 Hz), 6.65(d, 2H, J=9.7 Hz), 7.71(d, 2H, J=9.7 Hz), 9.69(s, 1H).

Workup

  1. customthe solution obtained
  2. customTo the reaction solution obtained
  3. customTo the mixture obtained
  4. stirringwhich was then stirred at room temperature for 2 hours and 30 minutes
  5. customThe resultant reaction solution
  6. concentrationwas concentrated
  7. dissolutiondissolved in 500 ml of ethyl acetate
  8. washby washing twice with 300 ml of water
  9. customThe organic layer thus formed
  10. dry with materialwas dried with anhydrous sodium sulfate
  11. concentrationfollowed by concentration under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by silica gel column chromatography (developing system: hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-972e4d2e99b240159eb8b66702f53313
Source dataset
uspto-grants-2000_04
Patent number
US06051722

Reaction notes

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