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

HRID 921727노트

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HRID 921727 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

HCID 86708610(+/-)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide수율 47.4%

시약·촉매·용매 2

HCID 180Acetone용매HCID 962Water용매

반응 조건

온도
0 °C

실험 절차

(+/−)-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.

후처리

  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

출처 및 근거

ORD 기록
ord-3feffb9721e0467285c7016e5b509613
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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