Methyl iodide → 1-Piperidinecarboxylic acid, 4-methoxy-3,3-dimethyl-, 1,1-dimethylethyl ester, (4S)-

HRID 80746

Reaktionsgleichung

Reaktionsgleichung von HRID 80746
[OH:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C:3]1([CH3:16])[CH3:15].[H-].[Na+].[CH3:19]I.[NH4+].[Cl-]>CN(C=O)C.O>[CH3:19][O:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C:3]1([CH3:16])[CH3:15]

Komponenten

7

Edukt 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 71244736tert-butyl (4S)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylate

Produkt 1

HCID 712448231-Piperidinecarboxylic acid, 4-methoxy-3,3-dimethyl-, 1,1-dimethylethyl ester, (4S)-

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (S)-tert-butyl 4-hydroxy-3,3-dimethylpiperidine-1-carboxylate (6.43 g, 28.0 mmol) in DMF (100 mL) at 0° C. was added NaH (60% dispersion in mineral oil, 2.24 g, 56.1 mmol), and the reaction mixture was stirred at room temperature for 15 min. Then, MeI (3.16 mL, 50.5 mmol) was added dropwise and the resulting mixture was stirred at room temperature for 1.5 h. The reaction mixture was then cooled to 0° C. and sat. aq. NH4Cl was added slowly and stirred for 5 min. The solution was warmed to room temperature and diluted with water (250 mL) and extracted with Et2O (3×200 mL). The combined organic extracts were washed with brine (100 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography (5-30% EtOAc/heptane) to provide (S)-tert-butyl 4-methoxy-3,3-dimethylpiperidine-1-carboxylate. 1H NMR (400 MHz, CDCl3) δ ppm 3.75 (br. s., 1 H), 3.41 (d, J=13.1 Hz, 1 H), 3.35 (s, 3 H), 3.09 (ddd, J=13.3, 9.3, 3.7 Hz, 1 H), 2.86 (dd, J=8.5, 3.7 Hz, 1 H), 2.80 (d, J=13.1 Hz, 1 H), 1.74-1.85 (m, 1 H), 1.48-1.59 (m, 1 H), 1.46 (s, 9 H), 0.94 (s, 3 H), 0.88 (s, 3 H).

Aufarbeitung

  1. stirringthe resulting mixture was stirred at room temperature for 1.5 h
  2. temperatureThe reaction mixture was then cooled to 0° C.
  3. stirringstirred for 5 min
  4. temperatureThe solution was warmed to room temperature
  5. extractionextracted with Et2O (3×200 mL)
  6. washThe combined organic extracts were washed with brine (100 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (5-30% EtOAc/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-ba04c87908e1437b9063b8adf26b3d84
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846656B2

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