Triphenylphosphine → 4-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

HRID 1020041

反応式

HRID 1020041 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:27]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[O:34][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 3

HCID 11776TriphenylphosphineHCID 2773253(2-(Benzyloxy)phenyl)boronic acidHCID 595089554-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

生成物 1

HCID 595091004-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester収率 62.2%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 10340Sodium Carbonate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

To a stirred mixture of 4-(6-chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (VIII) (0.74 g, 2.0 mmol) and 2-benzyloxyphenylboronic acid (0.50 g, 2.2 mmol) in saturated sodium carbonate solution (4 ml) and 1,4-dioxane (4 ml) was added palladium(II) acetate (0.09 g, 0.40 mmol) followed by triphenylphosphine (0.105 g, 0.400 mmol) at room temperature under an atmosphere of nitrogen. The resulting mixture was heated to reflux at 110° C. for one hour and monitored by TLC. The reaction mixture was filtered through a celite bed and the filtrate was extracted with ethyl acetate (3×100 ml). The organic layers were separated, combined, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative HPLC to afford 4-[6-(2-benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester (XVI) (0.65 g, 62%).

後処理

  1. temperatureThe resulting mixture was heated
  2. filtrationThe reaction mixture was filtered through a celite bed
  3. extractionthe filtrate was extracted with ethyl acetate (3×100 ml)
  4. customThe organic layers were separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC

出典と根拠

ORDレコード
ord-9048178595954ca5af9fb2080a2ed72c
出典データセット
uspto-grants-2014_05
特許番号
US08716296B2

関連ノート

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