Chloroacetyl chloride → (+/-)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide

HRID 921727Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921727
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([NH2:17])[C@H:13]([OH:18])[CH2:12]2)[C:9]=1[Cl:10])[C:5]#[N:6].C([O-])(=O)C.[K+].[Cl:24][CH2:25][C:26](Cl)=[O:27]>CC(C)=O.O>[NH2:1][C:2]1[C:9]([Cl:10])=[C:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([NH:17][C:26](=[O:27])[CH2:25][Cl:24])[C@H:13]([OH:18])[CH2:12]2)[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=1

Komponenten

6

Edukt 3

HCID 6577Chloroacetyl chlorideHCID 517044Potassium AcetateHCID 86708611(+/-)-3-amino-5-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-4-chlorobenzonitrile

Produkt 1

HCID 86708610(+/-)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamideAusbeute 47,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 180AcetoneLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(+/−)-3-amino-5-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-4-chlorobenzonitrile (prepared from Example 171D) (1.0 g, 3.75 mmol) and potassium acetate (0.736 g, 7.50 mmol) were dissolved in acetone (20 ml)+water (6 mL). The solution was cooled to 0° C. under nitrogen. Chloroacetic chloride (0.373 ml, 4.69 mmol) was added dropwise and the mixture stirred at 0° C. for 10 minutes, then at room temperature for 60 minutes. The reaction mixture was partitioned between EtOAc and aq. NaHCO3 solutions. The organic layer was washed with brine and dried over MgSO4. MgSO4 was removed by filtration and volatiles evaporated in vacuum to afford (+/−)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide (0.61 g); The material was used without further purification.

Aufarbeitung

  1. waitat room temperature for 60 minutes
  2. customThe reaction mixture was partitioned between EtOAc and aq. NaHCO3 solutions
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customMgSO4 was removed by filtration and volatiles
  6. customevaporated in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3feffb9721e0467285c7016e5b509613
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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