4-Toluenesulfonyl chloride → Indole piperidine ether

HRID 966498

Reaktionsgleichung

Reaktionsgleichung von HRID 966498
C[N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1CO.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(N(CC)CC)C.C[C:29]1[NH:30][C:31]2[C:36]([C:37]=1[C:38]([O:40][CH2:41][C:42]1C=CC=CC=1)=O)=[CH:35][C:34](O)=[CH:33][CH:32]=2.C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl>[NH:30]1[C:31]2[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:37]=[CH:29]1.[NH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:37][CH2:38][O:40][CH2:41][CH3:42]

Komponenten

7

Edukt 5

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 893941-Methyl-2-piperidinemethanolHCID 109239755-Hydroxy-2-methyl-1H-indole-3-carboxylic acid benzyl ester

Produkt 1

HCID 86587534Indole piperidine etherAusbeute 40,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-Methyl-2-piperidinemethanol (0.459 g, 3.580 mmol, 1 eq) was suspended in dry CH2Cl2 (5 mL). p-Toluenesulfonyl chloride (0.684 g, 3.580 mmol, 1 eq) and triethyl amine (1.00 mL, 7.160 mmol, 2 eq) were added. The reaction mixture was stirred at room temperature for 8 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was dissolved in dry acetonitrile (20 mL). 2-Methyl-3-benzyloxycarbonyl-5-hydroxyindole (1.005 g, 3.580 mmol, 1 eq) and Cs2CO3 (1.159 g, 3.580 mmol, 1 eq) were added. The reaction mixture was stirred and heated to reflux for 16 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was loaded on silica gel and chromatographed, eluting with ethyl acetate/methanol/triethyl amine (100/10/1). 0.200 g (15%) of the indole-piperidine ether was obtained as a brown solid. This was converted to the .HCl salt. LC/MS (ESI+) 393 (M+1); Anal. Calcd for C24H28N2O3.HCl.0.8H2O: C, 65.02; H, 6.96; N, 6.32; Found: C, 65.36; H, 7.02; N, 5.96.

Aufarbeitung

  1. customThen the reaction was quenched with saturated sodium bicarbonate
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. customAfter removing the solvent
  6. dissolutionthe residue was dissolved in dry acetonitrile (20 mL)
  7. stirringThe reaction mixture was stirred
  8. temperatureheated
  9. temperatureto reflux for 16 hours
  10. customThen the reaction was quenched with saturated sodium bicarbonate
  11. extractionextracted with ethyl acetate (3×)
  12. washThe combined organic phases were washed with brine
  13. dry with materialdried over Na2SO4
  14. customAfter removing the solvent
  15. customchromatographed
  16. washeluting with ethyl acetate/methanol/triethyl amine (100/10/1)

Quellen und Nachweise

ORD-Eintrag
ord-5192518f3d274fe4950779aab123386e
Quelldatensatz
uspto-grants-2005_10
Patentnummer
US06951848B2

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