Cesium carbonate → Methyl cis(+/-)-3-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)benzoate

HRID 43483

反応式

HRID 43483 の反応式
[CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6][NH:5][CH2:4]1.Br[C:21]1[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=1)[C:24]([O:26][CH3:27])=[O:25].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>O1CCOCC1.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:12]([O:11][C:10]([NH:9][C@H:8]1[CH2:7][CH2:6][N:5]([C:21]2[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=2)[C:24]([O:26][CH3:27])=[O:25])[CH2:4][C@H:3]1[O:2][CH3:1])=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

参加物

9

反応物 5

HCID 10796Cesium carbonateHCID 12070Methyl 3-bromobenzoateHCID 25517Ammonium ChlorideHCID 634876Binap, (A+-)-HCID 86648490Benzyl cis(+/-)-[3-methoxypiperidin-4-yl]carbamate

生成物 1

HCID 86648495Methyl cis(+/-)-3-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)benzoate収率 38.6%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Benzyl cis(±)-4-(3-methoxypiperidin-4-yl)-carbamate obtained by the method described in Example (40b) (0.5 g, 1.89 mmol) was dissolved in dioxane (20 ml) and DMF (6 mL). Methyl 3-bromobenzoate (0.35 g, 1.63 mmol), palladium acetate (39 mg, 0.17 mmol), BINAP (214 mg, 0.34 mmol) and cesium carbonate (1.35 g, 4.14 mmol) were added, and the mixture was stirred at 100° C. for 17 hours. Aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=90/10, 80/20, 0/100) to obtain 250.9 mg of the title compound as a yellow oily substance (39%).

後処理

  1. extractionfollowed by extraction with ethyl acetate
  2. washThen, the organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThereafter, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=90/10, 80/20, 0/100)

出典と根拠

ORDレコード
ord-28b69aec97334c68aa47dd0ddab44c50
出典データセット
uspto-grants-2013_09
特許番号
US08536197B2

関連ノート

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