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

HRID 43483

반응식

HRID 43483 반응식
[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

참가 물질

9

반응물 5

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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-28b69aec97334c68aa47dd0ddab44c50
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536197B2

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