Diisopropylethylamine → (1-Methylpiperidin-4-yl)methyl 4-(3-methylphenyl)piperazine-1-carboxylate

HRID 417955Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 417955
[C:1](=[O:21])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.Cl.Cl.[CH3:33][C:34]1[CH:35]=[C:36]([N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:37]=[CH:38][CH:39]=1>CN(C=O)C>[CH3:33][C:34]1[CH:35]=[C:36]([N:40]2[CH2:45][CH2:44][N:43]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][N:7]([CH3:10])[CH2:8][CH2:9]3)=[O:21])[CH2:42][CH2:41]2)[CH:37]=[CH:38][CH:39]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 831101-(m-Tolyl)piperazine dihydrochlorideHCID 57445006(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate2×

Produkt 1

HCID 42635254(1-Methylpiperidin-4-yl)methyl 4-(3-methylphenyl)piperazine-1-carboxylateAusbeute 13,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 1; 4.30 g, 14.6 mmol) was dissolved in DMF (50 mL). DIPEA (8.91 mL, 51.1 mmol) and 4-(3-methylphenyl)piperazine dihydrochloride (3.64 g, 14.6 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (500 mL) and then washed sequentially with 1 M aq NaOH solution (6×200 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (150 mL) and methyl isocyanate resin (1.0 g) was added and the reaction mixture shaken for 14 h, filtered and then concentrated in vacuo. The residue was purified by reverse phase 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 (1-methylpiperidin-4-yl)methyl 4-(3-methylphenyl)piperazine-1-carboxylate (0.65 g, 13.3%) as a pale yellow oil.

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (500 mL)
  3. washwashed sequentially with 1 M aq NaOH solution (6×200 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DCM (150 mL)
  7. additionmethyl isocyanate resin (1.0 g) was added
  8. stirringthe reaction mixture shaken for 14 h
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by reverse phase chromatography (gradient
  12. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  13. dissolutionThe resulting residue was dissolved in DCM (70 mL)
  14. stirringstirred with solid K2CO3 for 20 minutes
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-08175fd4836948fc8404c19277fd1eb4
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093248B2

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