Sodium hydride → (2R,5S)-4-Benzyl-2-methyl-5-(3-oxo-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1475473
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][C:2]1=[O:7].[H-].[Na+].[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23]Cl)[N:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:13])([CH3:12])[CH3:11]>CN(C=O)C>[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23][N:1]2[CH2:6][CH2:5][O:4][CH2:3][C:2]2=[O:7])[N:20]([CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:11])([CH3:12])[CH3:13]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 669533-MorpholinoneHCID 86724019tert-butyl (2R,5R)-4-benzyl-5-(chloromethyl)-2-methylpiperazine-1-carboxylate

Produkt 1

HCID 70980162(2R,5S)-4-Benzyl-2-methyl-5-(3-oxo-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterAusbeute 73,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

Morpholin-3-one (896 mg, 8.87 mmol) was added to a slurry of NaH (60% in mineral oil, 355 mg, 8.87 mmol) in DMF (10 mL) under N2. The suspension was stirred for 30 minutes at room temperature and then a solution of (2R,5R)-4-benzyl-5-chloromethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (2.0 g, 5.9 mmol) in DMF (10 mL) was slowly added. The resulting mixture was stirred at 65° C. for 2 h. The reaction was cooled to room temperature and partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over MgSO4 and concentrated in vacuo. Chromatography (50% EtOAc in petrol) gave the title compound (1.76 g) as a pale yellow gum. MS: [M+H]+=404.

Aufarbeitung

  1. stirringThe resulting mixture was stirred at 65° C. for 2 h
  2. temperatureThe reaction was cooled to room temperature
  3. custompartitioned between EtOAc and saturated aqueous NaHCO3
  4. dry with materialThe organic phase was dried over MgSO4
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-eb6113c5aef741abab9fbcc34ca8eda6
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018214B2

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