Sodium Bicarbonate → 4-{[2-(4-Chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

HRID 1473785Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473785
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10](Cl)=[O:11])=[C:4]([CH3:13])[CH:3]=1.C(=O)([O-])O.[Na+].[CH3:19][O:20][C:21]([C:23]1([NH:31][OH:32])[CH2:28][CH2:27][N:26]([O:29][CH3:30])[CH2:25][CH2:24]1)=[O:22]>C1COCC1>[CH3:19][O:20][C:21]([C:23]1([N:31]([C:10](=[O:11])[CH2:9][C:5]2[C:6]([CH3:8])=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:13])[OH:32])[CH2:28][CH2:27][N:26]([O:29][CH3:30])[CH2:25][CH2:24]1)=[O:22]

Komponenten

5

Edukt 3

HCID 516892Sodium BicarbonateHCID 11746058(4-Chloro-2,6-dimethyl-phenyl)-acetyl chlorideHCID 866574654-Hydroxyamino-1-methoxy-piperidine-4-carboxylic acid methyl ester

Produkt 1

HCID 584280914-{[2-(4-Chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (4-chloro-2,6-dimethyl-phenyl)-acetyl chloride (2.90 g, 13.4 mmol) in THF (25 ml) was added sodium hydrogen carbonate (1.90 g, 22.7 mmol) at 0° C., followed by 4-hydroxyamino-1-methoxy-piperidine-4-carboxylic acid methyl ester (preparation example 11, step 3; compound P4ii.2) (2.73 g, 13.4 mmol) dissolved in THF (25 ml) dropwise. The reaction mixture was stirred at 0° C. for 30 minutes, then further 30 minutes at room temperature. After completion of the reaction indicated by TLC and LC/MS, the reaction mixture was filtered and the residue (NaCl) washed with THF. The filtrate was concentrated to dryness and stirred several times with little amounts of an ether/hexane mixture (1:1) to remove side products. Finally, the compound was washed with ether to yield pure 4-{[2-(4-chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (compound P3ii.34) as white solid. Yield: 3.7 g, mp 228-231° C.

Aufarbeitung

  1. customfurther 30 minutes
  2. customat room temperature
  3. filtrationthe reaction mixture was filtered
  4. washthe residue (NaCl) washed with THF
  5. concentrationThe filtrate was concentrated to dryness
  6. stirringstirred several times with little amounts of an ether/hexane mixture (1:1)
  7. customto remove side products
  8. washFinally, the compound was washed with ether

Quellen und Nachweise

ORD-Eintrag
ord-48fea86930424b23aac87bba7b8082fe
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018135B2

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