Cesium carbonate → tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat

HRID 526377ノート

反応式

HRID 526377 の反応式
[C:1]([O:5][C:6](=[O:38])[CH2:7][C@H:8]([NH:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:37])[CH2:26][CH2:27][CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O-:36])=[O:35])[CH2:30][CH2:29]2)[CH2:20]1)=[O:18])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([OH:15])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[C:45]1([CH3:68])[CH:50]=[CH:49][C:48]([S:51]([O:54][CH2:55][CH2:56]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:53])=[O:52])=[CH:47][CH:46]=1>CN(C)C=O>[C:1]([O:5][C:6](=[O:38])[CH2:7][C@H:8]([NH:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:37])[CH2:26][CH2:27][CH:28]2[CH2:29][CH2:30][N:31]([C:34]([O:36][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:35])[CH2:32][CH2:33]2)[CH2:20]1)=[O:18])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([O:15][CH2:56][CH2:55][O:54][S:51]([C:48]2[CH:49]=[CH:50][C:45]([CH3:68])=[CH:46][CH:47]=2)(=[O:53])=[O:52])[CH:14]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 10796Cesium carbonate2 回HCID 228289Ethylene glycol ditosylate2 回HCID 1317355954-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

生成物 1

HCID 71609636tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat収率 154.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (200 mg, 0.34 mmol) were dissolved in N,N-dimethylformamide (39 mL). Cesium carbonate (277 mg, 0.85 mmol) and ethylene glycol bis-p-toluenesulfonate (188 mg, 0.51 mmol) were added. The mixture was stirred at room temperature for 4 hours, the addition of cesium carbonate (277 mg, 0.85 mmol) and ethylene glycol bis-p-toluenesulfonate (188 mg, 0.51 mmol) was repeated and stirring at 5° C. was continued for 17 hours. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with diethyl ether and ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 60%) to yield 207 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

後処理

  1. stirringstirring at 5° C.
  2. waitwas continued for 17 hours
  3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  4. extractionextracted with diethyl ether and ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 60%)

出典と根拠

ORDレコード
ord-e82a4768d3d6418cb7996574f111be72
出典データセット
uspto-grants-2016_05
特許番号
US09345793B2

反応ノート

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