Diisopropylethylamine → Piperidin-4-ylmethyl 4-(4-methylphenyl)piperazine-1-carboxylate

HRID 417953

Reaktionsgleichung

Reaktionsgleichung von HRID 417953
[C:1](=[O:27])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH:3](C(OC(C)(C)C)=O)[CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.Cl.Cl.[CH3:39][C:40]1[CH:45]=[CH:44][C:43]([N:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)=[CH:42][CH:41]=1>CN(C=O)C>[CH3:39][C:40]1[CH:41]=[CH:42][C:43]([N:46]2[CH2:51][CH2:50][N:49]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]3)=[O:27])[CH2:48][CH2:47]2)=[CH:44][CH:45]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 831121-(p-Tolyl)piperazine dihydrochlorideHCID 66650794(tert-Butoxycarbonyl)piperidin-4-ylmethyl 4-nitrophenyl carbonate2×

Produkt 1

HCID 42635252Piperidin-4-ylmethyl 4-(4-methylphenyl)piperazine-1-carboxylateAusbeute 50,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(tert-Butoxycarbonyl)piperidin-4-ylmethyl 4-nitrophenyl carbonate (Intermediate 2; 3.80 g, 10.0 mmol) was dissolved in DMF (100 mL). DIPEA (6.10 mL, 35.0 mmol) and 4-(4-methylphenyl)piperazine dihydrochloride (2.49 g, 10.0 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours and then concentrated in vacuo. The resulting residue was dissolved in EtOAc (300 mL) and washed with a 1 M aq Na2CO3 solution (6×200 mL), 10% citric acid solution (50 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in a mixture of DCM (100 mL) and TFA (25 mL), stirred for 48 hours and then concentrated in vacuo. The residue was purified by reverse phase column chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (70 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give piperidin-4-ylmethyl 4-(4-methylphenyl)piperazine-1-carboxylate (1.60 g, 44.6%) as a pale yellow solid.

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in EtOAc (300 mL)
  3. washwashed with a 1 M aq Na2CO3 solution (6×200 mL), 10% citric acid solution (50 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in a mixture of DCM (100 mL) and TFA (25 mL)
  7. stirringstirred for 48 hours
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by reverse phase column chromatography (gradient
  10. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  11. dissolutionThe resulting residue was dissolved in DCM (70 mL)
  12. stirringstirred with solid K2CO3 for 20 minutes
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-2ef148b727514ffd98f93fca5a2a73f1
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093248B2

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