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Cesium carbonate → Tert-butyl 2-(2-(benzyloxy)-5-(4-(dimethylamino)piperidin-1-yl)benzamido)-4-phenylbenzoate

HRID 454604
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HRID 454604 반응식
Cl.Cl.[CH3:3][N:4]([CH3:11])[CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:18]([O:25][C:26]1[CH:53]=[CH:52][C:51](Br)=[CH:50][C:27]=1[C:28]([NH:30][C:31]1[CH:43]=[C:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:41]=[CH:40][C:32]=1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(Cl)(Cl)Cl.O.C1(C)C=CC=CC=1>[CH2:18]([O:25][C:26]1[CH:53]=[CH:52][C:51]([N:8]2[CH2:9][CH2:10][CH:5]([N:4]([CH3:11])[CH3:3])[CH2:6][CH2:7]2)=[CH:50][C:27]=1[C:28]([NH:30][C:31]1[CH:43]=[C:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:41]=[CH:40][C:32]=1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

11

반응물 4

HCID 10796Cesium carbonate2회HCID 62657Potassium Phosphate, TribasicHCID 225914404-(Dimethylamino)piperidine dihydrochlorideHCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

생성물 1

HCID 66989971Tert-butyl 2-(2-(benzyloxy)-5-(4-(dimethylamino)piperidin-1-yl)benzamido)-4-phenylbenzoate수율 79.9%

시약·촉매·용매 6

HCID 167845palladium(II) acetate촉매3회HCID 9811564Bis(dibenzylideneacetone)palladium촉매3회HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매3회HCID 962Water용매HCID 1140Toluene용매HCID 6212Chloroform용매

실험 절차

4-(Dimethylamino)piperidine dihydrochloride (0.11 g), cesium carbonate (0.44 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg), and palladium(II) acetate (1.2 mg) were added to a toluene (2.3 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 3 hours. The reaction mixture was cooled to room temperature, and cesium carbonate (0.13 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg), and palladium(II) acetate (1.2 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 7 hours. The reaction mixture was cooled to room temperature, and tripotassium phosphate (0.29 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg), and palladium(II) acetate (1.2 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 2 hours and 30 minutes. The reaction mixture was cooled to room temperature, and water and chloroform were added thereto. The insoluble substance was removed by filtration. The organic layer was separated and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol] to obtain 0.13 g of tert-butyl 2-(2-(benzyloxy)-5-(4-(dimethylamino)piperidin-1-yl)benzamido)-4-phenylbenzoate.

후처리

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 3 hours
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 7 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. temperatureby heating
  7. temperatureto reflux under a nitrogen atmosphere for 2 hours and 30 minutes
  8. temperatureThe reaction mixture was cooled to room temperature
  9. customThe insoluble substance was removed by filtration
  10. customThe organic layer was separated
  11. dry with materialdried over anhydrous sodium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol]

출처 및 근거

ORD 기록
ord-62e47d063d614d2489678a361990ba65
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08492582B2

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