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

HRID 1430905ノート

反応式

HRID 1430905 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

(+/−)-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 solution. 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.

後処理

  1. waitat room temperature for 60 minutes
  2. customThe reaction mixture was partitioned between EtOAc and aq. NaHCO3 solution
  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

出典と根拠

ORDレコード
ord-4cd9ba229e34441f8ec0522a3c120e76
出典データセット
uspto-grants-2015_01
特許番号
US08940736B2

反応ノート

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